cssi/SciSciGPT-SciSciNet huggingface dataset:
Adaptive and Robust Methods of Reconstruction (ARMOR) for Thermoacoustic Tomography

In this paper, we present new adaptive and robust methods of reconstruction (ARMOR) for thermoacoustic tomography (TAT), and study their performances for breast cancer detection. TAT is an emerging medical imaging technique that combines the merits of high contrast due to electromagnetic or laser stimulation and high resolution offered by thermal acoustic imaging. The current image reconstruction methods used for TAT, such as the delay-and-sum (DAS) approach, are data-independent and suffer from low-resolution, high sidelobe levels, and poor interference rejection capabilities. The data-adaptive ARMOR can have much better resolution and much better interference rejection capabilities than their data-independent counterparts. By allowing certain uncertainties, ARMOR can be used to mitigate the amplitude and phase distortion problems encountered in TAT. The excellent performance of ARMOR is demonstrated using both simulated and experimentally measured data.
Genetics of isolated growth hormone deficiency.

When a child is not following the normal, predicted growth curve, an evaluation for underlying illnesses and central nervous system abnormalities is required, and appropriate consideration should be given to genetic defects causing growth hormone (GH) deficiency (GHD). Because Insulin−like Growth Factor−I (IGF−I) plays a pivotal role, GHD could also be considered as a form of IGF−I deficiency (IGFD). Although IGFD can develop at any level of the GH−releasing hormone (GHRH)−GH−IGF axis, a differentiation should be made between GHD (absent to low GH in circulation) and IGFD (normal to high GH in circulation). The main focus of this review is on the GH gene, the various gene alterations and their possible impact on the pituitary gland. However, although transcription factors regulating the pituitary gland development may cause multiple pituitary hormone deficiency, they may present initially as GHD. Conflict of interest:None declared.
Growth and Governance: A Rejoinder

Kurtz and Schrank (hereafter KS) begin their defense by accusing us of “abandoning” our measure of Government Effectiveness in favor of other indicators such as Rule of Law. All we noted in our original response, and reiterate here, is that we find KS’s exclusive emphasis on this one particular dimension of governance to be idiosyncratic and not shared by the large economics literature on institutions and growth. We also note that we discussed all six of our governance indicators in our response simply because the critiques that KS raise of government effectiveness, notably potential respondent biases and halo effects, could equally well be applied to our other indicators. We think it important to demonstrate the scarcity of empirical support for these critiques for all six of our governance indicators.
Reprint of: The Deadman Theory of Suture Anchors: Observations Along a South Texas Fence Line

Abstract Suture anchors are being increasingly reported as a means of fixation of torn rotator cuff tendons to bone. The author has developed a mechanical model for the suture anchor–rotator cuff construct based on an analogy to the deadman system used to stabilize a corner fence post. Using this model, one can demonstrate a mechanically favorable angle of insertion of the suture anchor (θ 1 ) such that the anchor's pullout strength is increased at low angles of θ 1 . In addition, the angle that the suture makes with the direction of pull of the rotator cuff (θ 2 ) has a direct effect on tension in the suture. A low angle of θ 2 minimizes the total tension in the suture, thereby minimizing the chance of suture breakage.
Successful turnaround strategies

Purpose – The purpose of this paper is to help CEOs pick the best turnaround strategy.Design/methodology/approach – The paper reviews a key research study on firms in turnaround situations.Findings – The study finds that turnaround strategy must fit the cause of the firm's problem.Practical implications – The paper is useful in helping senior managers avoid a common problem.Originality/value – The paper focuses attention on the key to turnaround success. It highlights an academic research study with a rare nugget of insight for CEOs. This paper has not been published elsewhere.
Equations of Motion in Classical Mechanics

In classical mechanics one studies the motions of objects on a macroscopic level. These motions, of a particle or a system of particles, of the planets around the sun, or of a pendulum, for example, are governed by differential equations. These equations, or their solutions, are called equations of motion, which in earliest form go back to Newton. Other forms are due to Lagrange, Hamilton, Jacobi, and others.
Duration to Admission and Hospital Transfers Affect Facility Rankings from the Postacute 30-Day Rehospitalization Quality Measure.

Objective To examine changes in facility-level risk-standardized rehospitalization rankings for postacute inpatient rehabilitation facilities after modifying two model parameters. Data Sources We used national Medicare enrollment, claims, and assessment data to study 522,260 patients discharged from inpatient rehabilitation in fiscal years 2010–2011. Study Design We calculated risk-standardized 30-day unplanned rehospitalization rates for 1,135 inpatient rehabilitation facilities using four approaches. The first model replicated the current postacute risk-standardization methodology and included patients discharged from acute hospitals up to 30 days prior to postacute admission and excluded patients transferred directly back to acute hospitals following rehabilitation. Our alternative models excluded patients with delayed admissions (>1 day between acute discharge and postacute admission) and counted direct transfers back to acute as rehospitalizations. Principal Findings Excluding patients with delayed admissions and counting direct transfers back to acute care as rehospitalizations substantially impacted rankings of more than half the postacute providers: 29 percent had better and 27 percent had worse quintile rankings. Conclusions Changing the timeframes for duration to admission and rehospitalization will have profound effects on postacute provider quality performance ratings. Reporting rehospitalization rates is an important issue with the explicit goal of improving the quality of postacute care. Research is needed to understand and minimize potential unintended consequences of this quality metric.
Biocompatibility of "On-command" dissolvable tympanostomy tube in the rat model.

Objectives/Hypothesis A prototype tympanostomy tube, composed of polybutyl/methyl methacrylate-co-dimethyl amino ethyl methacrylate (PBM), was tested to 1) evaluate the effect of PBM tubes on rat dermis as a corollary for biocompatibility and (2) to observe the efficacy of dissolution with isopropyl alcohol (iPrOH) and ethanol (EtOH). Study Design Original animal experiment and bench testing. Methods A two-part study was conducted to assess biocompatible substance with inducible dissolvability as a critical characteristic for a newly engineered tympanostomy tube. First, tympanostomy tubes were inserted subcutaneously in 10 rats, which served as an animal model for biosafety, and compared to traditional tubes with respect to histologic reaction. Tissue surrounding the PBM prototype tubes was submitted for histopathology and demonstrated no tissue reactivity or signs of major inflammation. In the second part, we evaluated the dissolvability of the tube with either isopropyl alcohol, ethanol, ofloxacin, ciprodex, water, and soapy water. PBM tubes were exposed to decreasing concentrations of iPrOH and EtOH with interval qualitative assessment of dissolution. Results Histologic examination did not reveal pathology with PBM tubes. Concentrations of at least 50% iPrOH and EtOH dissolve PBM tubes within 48 hours, whereas concentrations of at least 75% iPrOH and EtOH were required for dissolution when exposure was limited to four 20-minute intervals. Conclusions PBM is biocompatible in the rat model. Additionally, PBM demonstrates rapid dissolution upon alcohol-based stimuli, validating the proof-of-concept of dissolvable on-command or biocommandible ear tubes. Further testing of PBM is needed with a less ototoxic dissolver and in a better simulated middle ear environment before testing can be performed in humans. Level of Evidence NA Laryngoscope, 2016
Low molecular weight organogelators derived from threefold symmetric tricarbamates

Abstract A group of new low molecular weight organogelators based on threefold symmetric tricarbamate were synthesized and characterized. The tricarbamates with long alkyl chains were able to gelate a wide range of polar and nonpolar organic solvents such as acetonitrile and cyclohexane, generally at concentrations lower than 20 g/L. The best organogel formation was obtained using a threefold symmetric tricarbamate in n -dodecane, in which a sufficiently transparent gel was formed at the critical gelation concentration 1 g/L. Intermolecular hydrogen bonding by the tricarbamate in a nonpolar solvent benzene- d 6 was indicated by 1 H NMR spectra. Its maximum UV absorption was 11 nm higher in chloroform than in n -dodecane, and this red shift indicated increased conjugation between the benzene core and the carbamate substituents, which confirmed a change in its conformation from nonpolar to polar solvent. The self-assembling behavior of the tricarbamate in dilute solutions was investigated by TEM. Fiber-like networks were observed in a large range of solution concentrations.
Effectiveness and Cost-Effectiveness of Endoscopic Screening and Surveillance.

Guidelines for the screening and surveillance of Barrett's esophagus continue to evolve as the incidence of esophageal adenocarcinoma increases, identification of individuals at highest risk for cancer improves, and management of dysplasia evolves. This article reviews related studies and economic analyses. Advances in diagnosis offer promising strategies to help focus screening efforts on those individuals who are most likely to develop esophageal adenocarcinoma.
Phase separation of BuGZ promotes Aurora A activation and spindle assembly

The spindle matrix has been proposed to facilitate mitotic spindle assembly. In this issue, Huang et al. (2018. J. Cell Biol. https://doi.org/10.1083/jcb.201706103) show that the spindle matrix protein BuGZ is sufficient to form micron-scale compartments that recruit and activate Aurora A, a critical kinase for spindle assembly.
Sampling for Single and Multi-Mode Surveys Using Address-Based Sampling

Nearly all households in the USA have a mailing address that is used by the United States Postal Service (USPS) for mail delivery and these addresses can be used as a sampling frame that has good coverage properties. The Delivery Sequence File (DSF), which is maintained by the USPS, provides a convenient basis for conducting address-based sampling (ABS). As a sampling frame, the DSF can be used to conduct multi-mode surveys, particularly where telephone numbers can be matched to the DSF. This chapter highlights the value of the DSF for single and multi-mode surveys and also outlines some of the potential problems with using the DSF as a sampling frame.
Serum Albumin Predicts Survival and Postoperative Course Following Surgery for Geriatric Hip Fracture.

BACKGROUND Serum albumin level is the most well-established serum marker of malnutrition, with a serum albumin concentration <3.5 g/dL considered to be suggestive of malnutrition. The purpose of this study was to test if serum albumin level is associated with death, specific postoperative complications (e.g., pneumonia), length of hospital stay, and readmission following a surgical procedure for geriatric hip fracture. METHODS A retrospective cohort study of geriatric patients (≥65 years of age) undergoing a hip fracture surgical procedure as part of the American College of Surgeons National Surgical Quality Improvement Program was conducted. Outcomes were compared between patients with and without hypoalbuminemia. All comparisons were adjusted for baseline and procedural differences between populations, and patients with missing serum albumin concentration were included in analyses using a missing data indicator. RESULTS There were 29,377 geriatric patients undergoing a hip fracture surgical procedure who met inclusion criteria; of these patients, 17,651 (60.1%) had serum albumin available for analysis. The prevalence of hypoalbuminemia was 45.9%. Following adjustment for baseline and procedural characteristics, the risk of death was inversely associated with serum albumin concentration as a continuous variable (adjusted relative risk, 0.59 [95% confidence interval (CI), 0.53 to 0.65]; p < 0.001). In comparison with patients with normal albumin concentration, patients with hypoalbuminemia had higher rates of death (9.94% compared with 5.53% [adjusted relative risk, 1.52 (95% CI, 1.37 to 1.70); p < 0.001]), sepsis (1.19% compared with 0.53% [adjusted relative risk, 1.92 (95% CI, 1.36 to 2.72); p < 0.001]), and unplanned intubation (2.64% compared with 1.47% [adjusted relative risk, 1.51 (95% CI, 1.21 to 1.88); p < 0.001]). The mean length of stay (and standard deviation) was longer among patients with hypoalbuminemia at 5.67 ± 4.68 days compared with those without hypoalbuminemia at 4.99 ± 3.95 days; the adjusted difference was 0.50 day (95% CI, 0.38 to 0.63 day; p < 0.001). However, the rate of readmission did not differ (p = 0.054) between patients with hypoalbuminemia (10.91%) and those without hypoalbuminemia (9.03%); the adjusted relative risk was 1.10 (95% CI, 1.00 to 1.21). CONCLUSIONS Hypoalbuminemia is a powerful independent risk factor for mortality following a surgical procedure for geriatric hip fracture. These data suggest that further investigation into postoperative nutritional supplementation is warranted to decrease the risk of complications. LEVEL OF EVIDENCE Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Risk and survival of patients with medullary thyroid cancer: National perspective.

Abstract Background Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor account for 1–2% of thyroid cancer. In this study, we aim to examine the characteristics and survival of patients with MTC. Methods A retrospective cohort study utilizing the National Cancer Data Base, 2004–2014. The study population included adults with either MTC (cases) or with differentiated thyroid cancer (DTC) (controls). Results A total of 2,776 MTC and 171,631 DTC patients were included. The median follow-up time for MTC was 55.5 months (interquartile range: 31.2–84.6 months). As compared to DTC, patients with MTC were more likely to be ≥ 45-year old, male, and Black (p Conclusions Neck dissection performed on patients with clinically N0 neck, is important for accurate staging and associate with improved survival in advanced stages. Thyroidectomy and neck dissection in stage IV not only have palliative role but also add survival advantage.
EVIDENCE FOR A PROTON PUMP IN RAT LIVER LYSOSOMES

Acidification of lysosomes has been considered as a possible energy-dependent step of protein degradation. Measurement of ATPase activity revealed the presence of a membrane-bound enzyme in rat liver lysosomes. The activity is stimulated by gramicidin plus potassium ion and carbonylcyanide-m-chlorophenylhydrazone. The possibility that this ATPase activity represents an ATP-driven proton pump was supported by two observations. First, the fluorescence of anilinonaphthalene sulfonate bound to lysosomes was enhanced by addition of MgATP and the enhancement was reversed by carbonylcyanide-m-chlorophenylhydrazone. Second, the uptake of methylamine by lysosomes was stimulated by MgATP but not by MgADP, MgAMP, or MgEDTA.
Overview of IBSNAT

The objective of the IBSNAT or International Benchmark Sites Network for Agrotechnology Transfer project was to apply systems analysis and simulation to problems faced by resource-poor farmers in the tropics and sub-tropics, specifically in the area of evaluating new and untried agricultural technologies. Outputs from the project include the portable decision support system, DSSAT, the minimum data set necessary to drive the system and a collaborative network composed of an international, interdisciplinary team of scientists from more than 25 countries. Network members joined together to develop, assemble, test and use one of the most widely used decision support systems in the world today. The decision support system products enable users to match the biological requirements of crops to the physical characteristics of land to provide them with management options for improved land use decisions.
Image enhancement: probability versus fuzzy expert systems

The field of image enhancement is being used in various areas and disciplines. Advances in computers, microcontrollers, and digital signal processing (DSP) boards have opened new horizons to digital image processing and many avenues to the design and implementation of new innovative techniques. This chapter compares image enhancement, via modification of the probability density function of gray levels, with new techniques that involve the use of knowledge-based (fuzzy expert) systems capable of mimicking the behavior of a human expert.
The meniscus on the outside of a circular cylinder: From microscopic to macroscopic scales

We systematically study the meniscus on the outside of a small circular cylinder vertically immersed in a liquid bath in a cylindrical container that is coaxial with the cylinder. The cylinder has a radius R much smaller than the capillary length, κ-1, and the container radius, L, is varied from a small value comparable to R to ∞. In the limit of L≪κ-1, we analytically solve the general Young-Laplace equation governing the meniscus profile and show that the meniscus height, Δh, scales approximately with Rln(L/R). In the opposite limit where L≫κ-1,Δh becomes independent of L and scales with Rln(κ-1/R). We implement a numerical scheme to solve the general Young-Laplace equation for an arbitrary L and demonstrate the crossover of the meniscus profile between these two limits. The crossover region has been determined to be roughly 0.4κ-1≲L≲4κ-1. An approximate analytical expression has been found for Δh, enabling its accurate prediction at any values of L that ranges from microscopic to macroscopic scales.
Calling HCI professionals into health research: patient safety and health equity at stake

The paper describes the need for expansion of the role of human-computer interaction (HCI) professionals into the field of e-health interventions, including games, virtual reality, and social media. Authors summarize critical practical, methodological, and philosophical gaps that prevent further synergy and collaboration. The necessity for closing these gaps is guided through a discussion on ethics and a health equity framework.
Abstract TP348: Early Palliative Care Consultation in Acute Stroke

Introduction: Despite great strides in management, stroke remains a significant cause of disability and death. Families are often abruptly confronted with critical decisions about end-of-life care;...
Cannot Find the Ureter

Ureteral injuries can have devastating consequences for the patient. Unfortunately, patient- and disease-related factors can create conditions difficult for proper identification. Here we review some methods to help identify the ureter.
Anthropogenic biases in chemical reaction data hinder exploratory inorganic synthesis

Most chemical experiments are planned by human scientists and therefore are subject to a variety of human cognitive biases1, heuristics2 and social influences3. These anthropogenic chemical reaction data are widely used to train machine-learning models4 that are used to predict organic5 and inorganic6,7 syntheses. However, it is known that societal biases are encoded in datasets and are perpetuated in machine-learning models8. Here we identify as-yet-unacknowledged anthropogenic biases in both the reagent choices and reaction conditions of chemical reaction datasets using a combination of data mining and experiments. We find that the amine choices in the reported crystal structures of hydrothermal synthesis of amine-templated metal oxides9 follow a power-law distribution in which 17% of amine reactants occur in 79% of reported compounds, consistent with distributions in social influence models10-12. An analysis of unpublished historical laboratory notebook records shows similarly biased distributions of reaction condition choices. By performing 548 randomly generated experiments, we demonstrate that the popularity of reactants or the choices of reaction conditions are uncorrelated to the success of the reaction. We show that randomly generated experiments better illustrate the range of parameter choices that are compatible with crystal formation. Machine-learning models that we train on a smaller randomized reaction dataset outperform models trained on larger human-selected reaction datasets, demonstrating the importance of identifying and addressing anthropogenic biases in scientific data.
Religion in the University

As the Noah Potter Professor Emeritus of Philosophical Theology at Yale University and author of numerous books on the university, Nicholas Wolterstorff’s influence on higher education cannot be ov...
Heterogeneity in Prescription Opioid Pain Reliever Misuse Across Age Groups: 2015-2017 National Survey on Drug Use and Health.

Prescription opioid misuse among older adults has received little attention to date. Potential age variation in characteristics of and motivations for prescription opioid misuse has not been fully characterized yet has important implications for preventing diversion and misuse. To examine (1) age-specific patterns of source of misused prescription opioid pain relievers and motives for misuse and (2) age-specific and source-specific associations with opioid use disorder (OUD), heroin use, benzodiazepine misuse, and OUD treatment utilization. Cross-sectional study using 3 waves (2015–2017) of the National Survey on Drug Use and Health (68% average response rate) Respondents aged 12 and older with past-year prescription opioid pain reliever misuse (n = 8228) Source for the most-recently misused prescription pain reliever (categorized as medical, social, or illicit/other), motive for last episode of misuse, OUD, heroin use, benzodiazepine misuse, and OUD treatment. Adults 50 and older comprised approximately 25% of all individuals reporting past-year prescription opioid misuse. A social source was most common for individuals under age 50 while a medical source was most common for individuals 50 and older. The most commonly reported motive for misuse was to “relieve physical pain”; the frequency of this response increased across age groups (47% aged 12–17 to 87% aged 65+). Among adults age 50 and older with prescription opioid misuse, 17% met criteria for OUD, 15% reported past-year benzodiazepine misuse, and 3% reported past-year heroin use. Physicians continue to be a direct source of prescription opioids for misuse, particularly for older adults. Ongoing clinical initiatives regarding optimal opioid prescribing practices are needed in addition to effective non-opioid strategies for pain management. Clinical initiatives should also include screening adult and adolescent patients for non-medical use of prescription opioids as well as improving access to OUD treatment for individuals of all ages.
Exponentially small splitting: A direct approach

Abstract In this paper, we go beyond what was proposed in theory by Melnikov ( [15] ) to introduce a practical method to calculate the high order splitting distances of stable and unstable manifold in time-periodic equations. Not only we derive integral formula for splitting distances of all orders, but also we develop an analytic theory to evaluate the acquired multiple integrals. We reveal that the dominance of the exponentially small Poincare/Melnikov function for equations of high frequency perturbation is caused by a certain symmetry embedded in the kernel functions of high order Melnikov integrals. This symmetry is beheld by many non-Hamiltonian equations.
Mechanistic modelling of ammonia emission from laying hen manure at laboratory scale

A mechanistic model was developed for estimating ammonia (NH3) emission from laying hen manure based on measurements from a laboratory-scale wind-tunnel experiment. Ammonia emissions were measured continuously for 3–6 d from manure samples under 17 different combinations of air temperatures (20.0–33.5°C) and air velocities (0.25–1.17 m s−1). The convective mass transfer coefficient, KG, which was estimated using chamber air velocity and temperature, averaged 6.81 ± 4.04 m h−1 and ranged from 0.47 to 16.76 m h−1 (R2 = 0.91). The average dissociation constant ratio α, estimated as a function of manure pH and moisture content, was 0.175 ± 0.103 (R2 = 0.81). Total ammonia nitrogen (TAN) has been reported in the literature as a key factor influencing NH3 emission from manure, however, its influence observed in these laboratory studies was statistically insignificant (p = 0.16). The model was developed using two independent groups of experimental data, one for model training, and the other for model validation. The model had adequate accuracy in estimating NH3 emission from layer manure with normalised mean squared error (NMSE) of 0.08 and R2 of 0.79. Sensitivity analyses suggested that NH3 emission was most sensitive to manure pH, followed by air temperature and air velocity. The results can serve as a basis for developing a reliable, practical and simple NH3 emission estimation model for determining compliance with NH3 emission regulations and developing effective mitigation strategies.
Heterocycles in the Treatment of Neglected Tropical Diseases.

BACKGROUND Neglected Tropical Diseases (NTDs) affect a huge population of the world and the majority of the victims belong to the poor community of the developing countries. Until now, the World Health Organization (WHO) has identified 20 tropical diseases as NTDs that must be addressed with high priority. However, many heterocyclic scaffolds have demonstrated potent therapeutic activity against several NTDs. OBJECTIVE There are three major objectives: (1) To discuss the causes, symptoms, and current status of all the 20 NTDs; (2) To explore the available heterocyclic drugs, as well as their mechanisms of action (if known), that are being used to treat NTDs; (3) To develop general awareness on NTDs among the medicinal/health research community and beyond. METHODS The 20 NTDs have been discussed according to their alphabetic orders along with the possible heterocyclic remedies. The current status of treatment with an emphasis on the heterocyclic drugs (commercially available and investigational) has been outlined. In addition, a brief discussion of the impacts of NTDs on socio-economic conditions is included. RESULTS NTDs are often difficult to diagnose and the problem is worsened by the unhealthy hygiene, improper awareness, and inadequate healthcare in the developing countries where these diseases primarily affect poor people. The statistics include the duration of suffering, the number of individuals affected, and access to healthcare and medication. The mechanisms of action of various heterocyclic drugs, if reported, have been briefly summarized. CONCLUSION Scientists and pharmaceutical corporations should allocate more resources to reveal the in-depth mechanism of action of many heterocyclic drugs that are currently being used for the treatment of NTDs. Analysis of current heterocyclic compounds and the development of new medications can help in the fight to reduce/remove the devastating effects of NTDs. An opinion-based concise review has been presented. Based on the available literature, this is the first attempt to present all the 20 NTDs and related heterocyclic compounds under the same umbrella.
Chapter 7 – Pharmacogenomics

Over the past few decades, advances in the field of pharmacogenomics have made a significant impact in delineating the genetic factors that are responsible for variable drug responses. This has broadened the scope of implementing pharmacogenomic knowledge not only to clinical practices but also for drug discovery. Ayurveda has been practicing the concept of personalized medicine for more than 4000 years and it can be explored for this purpose. The insights from the science of Ayurveda may offer us new understandings of human biology and its greater potential for creating designer medicines. In this chapter, we discuss recent advances in the field in the pharmacogenomics, its potential use in clinical practice, and its translation into individualized medicine. We will further discuss how integrating evidence-based innovative initiatives such as Ayugenomics can potentially facilitate steps toward overcoming some of the challenges to achieve the ultimate goal of individualized medicine.
Free Exercise Partisanship

This Article presents new data that shows that, in contrast to earlier periods, judicial decision-making in free exercise cases now tracks political affiliation to a significant degree. The trend toward increased free exercise partisanship is starkly manifested by free exercise cases related to the pandemic: a survey of every federal court decision pertaining to challenges to prohibitions of religious gatherings during the pandemic reveals that 0% of Democrat-appointed judges have sided with religious plaintiffs, the majority (66%) of Republican-appointed judges have sided with religious plaintiffs, and 82% of Trump-appointed judges have sided with religious plaintiffs. But while religious challenges to COVID-19 lockdown orders have thrown free exercise partisanship into sharp relief, the trend of increased partisanship in free exercise jurisprudence actually pre-dates the onset of the pandemic. This Article makes several contributions. One is empirical: it offers an original dataset that tracks every free exercise case from the last five years (picking up where previous surveys of free exercise cases left off). One is historical: it tells the story of how free exercise became politically controversial. Another is doctrinal: it reveals the deep ambiguity at the heart of free exercise doctrine, which this Article argues has enabled the rise in free exercise partisanship. Finally, one is jurisprudential: it shows the relationship between doctrinal clarity and partisanship, which has implications for constitutional law writ large.
Correction to: Heat shock protein-90alpha (Hsp90α) stabilizes hypoxia-inducible factor-1α (HIF-1α) in support of spermatogenesis and tumorigenesis.

Hypoxia-inducible factor-1 (HIF-1), a master transcriptional factor for protecting cells from hypoxia, plays a critical role in spermatogenesis and tumorigenesis. For the past two decades, numerous small molecule inhibitors that block mRNA synthesis, protein translation, or DNA binding of HIF-1α have entered clinical trials. To date, few have advanced to FDA approval for clinical applications due to limited efficacy at their toxicity-tolerable dosages. New windows for developing effective and safe therapeutics require better understanding of the specific mechanism of action. The finding that a chaperone-defective mutant heat shock protein-90-alpha (Hsp90α) blocks spermatogenesis, a known hypoxia-driven process in mouse testis prompted us to focus on the role of Hsp90α in HIF-1α. Here we demonstrate that Hsp90α gene knockout causes a dramatic reduction of the high steady-state level of HIF-1α in the testis, blocking sperm production and causing infertility of the mice. In HIF-1α-dependent tumor cells, we found that Hsp90α forms protein complexes with hypoxia-elevated HIF-1α and Hsp90α knockout prevents hypoxia-induced HIF-1α accumulation. In contrast, downregulation of Hsp90β had little effect on hypoxia-induced accumulation of HIF-1α. Instead, Hsp90β protects signaling molecules responsible for cellular homeostasis from assault by 17-AAG (17-N-allylamino-17-demethoxygeldanamycin), a general ATPase inhibitor of both Hsp90α and Hsp90β. Since targeting Hsp90β gene is lethal in both cultured cells and in mice, our new finding explains the toxicity of the previous inhibitor trials and identifies the specific binding of Hsp90α to HIF-1α as a new therapeutic window for developing safer and more effective treatment of male infertility and cancer.
The Pandemic and the Costs of an Unhealthy America

On January 30, 2020, the World Health Organization (WHO) declared the outbreak of the disease COVID-19 as a “public health emergency of international concern.” The announcement got little traction in the United States. Although professional epidemiologists were worried, there was little expression of official government concern. The United States soon emerged as a national hotspot with a large number of cases and reported deaths. There was a lack of coordinated response, a failure to take the virus as a serious threat, and an almost criminal lack of vital medical equipment. The pandemic revealed a health system geared to providing care for the affluent, a hollowing out of the state as a provider of social welfare, and a fragmented government public health system undermined by hyper-partisan politics.
Epistasis Is a Major Determinant of the Additive Genetic Variance in Mimulus guttatus.

The influence of genetic interactions (epistasis) on the genetic variance of quantitative traits is a major unresolved problem relevant to medical, agricultural, and evolutionary genetics. The additive genetic component is typically a high proportion of the total genetic variance in quantitative traits, despite that underlying genes must interact to determine phenotype. This study estimates direct and interaction effects for 11 pairs of Quantitative Trait Loci (QTLs) affecting floral traits within a single population of Mimulus guttatus. With estimates of all 9 genotypes for each QTL pair, we are able to map from QTL effects to variance components as a function of population allele frequencies, and thus predict changes in variance components as allele frequencies change. This mapping requires an analytical framework that properly accounts for bias introduced by estimation errors. We find that even with abundant interactions between QTLs, most of the genetic variance is likely to be additive. However, the strong dependency of allelic average effects on genetic background implies that epistasis is a major determinant of the additive genetic variance, and thus, the population’s ability to respond to selection.
Fiduciary Duties of Controlling Shareholders: A Comparative View

Both directors and controlling shareholders are vested with the power to exercise control over the property of others. While the common law has recognized strict fiduciary duties binding the directors of a company,' it has refused to impose a general fiduciary duty on controlling shareholders. The voting power of the majority shareholders has been restricted, on the other hand, by the common law in two categories of cases: where a resolution relates to the alteration of the company's memorandum and articles of association and where a resolution is tainted by "fraud on the minority." Israeli corporate law, though generally based on English company law,2 has recently departed from the English view with regard to the fiduciary duties of controlling shareholders. English law denies the imposition of a fiduciary duty on controlling shareholders to minority shareholders. Israeli law, however, has veered toward the American view, which favours imposing a fiduciary duty on controlling shareholders. The purpose of this article is to trace the development of Israeli law in this field, comparing it with English and American law. Further, it shall examine the extent to which a general fiduciary duty should be recognized on the part of controlling shareholders in England and in Israel. This examination will explore the underlying rationale for the recognition of a fiduciary duty in this field. By focusing on the relevant statutory provisions of England and Israel, this article will shed light on the attitudes of these countries' legislatures towards a fi-
Motivating Hume's natural virtues

Many commentators propose that Hume thinks that we are not or should not be motivated to perform naturally virtuous actions from moral sentiments. I take issue with this interpretation in this paper, arguing that Hume fully incorporates the moral sentiments into his understanding of how human beings act when it comes to the natural virtues and that he does not see the moral sentiments as a problematic kind of motivation that threatens or weakens the virtuous status of the action.
Teleost urophysis: I. Bioassay of an active urophysial principle on the isolated urinary bladder of the Rainbow Trout, Salmo gairdnerii

Abstract A potent smooth muscle-contracting substance was found in aqueous and acid extracts of teleost urophyses. An assay procedure for the estimation of this substance was devised utilizing the isolated urinary bladder of the Rainbow Trout ( Salmo gairdnerii ). Rhythmic contractions of the trout bladder filled with 1 5 trout-Ringer's solution and immersed in an organ bath containing 10 ml of trout-Ringer's solution, were recorded on paper by means of a pressure transducer-amplifier. Reproducible responses were obtained with as little as 0.004 of a urophysis/ml bath fluid. Preparation of a urophysial laboratory standard is described. Estimations of the bladder-contracting substance in urophysial extracts of several teleost species showed that concentration of activity was considerably lower in salmonids (Rainbow Trout and Chinook Salmon) than in the mudsucker Gillichthys mirabilis, Tilapia mossambica , or the mullet Mugil cephalus . More activity appeared to be present in seawater mullet than in freshwater mullet, especially when related to body weight.
What does it all mean to you

Nearly 20 years ago, I introduced a special series of articles for Trends in Neurosciences (5:295, 1982) that sought to illustrate some of the then-latest developments in molecular neuroscience. That was the time when neuroscientists were beginning to borrow heavily from the nascent field of
ISAR imaging of a windmill - measurement and simulation

Inverse synthetic aperture radar (ISAR) images of a windmill are presented. In-situ measurement data of an 18- blade windmill are collected using an ultra-wideband radar. The measured signatures are compared to simulation results based on physical optics. The backscattering phenomenology is examined in the sinogram, spectrogram, and ISAR image domains. In addition, a composite image is generated from multiple ISAR snapshots to reveal the entire windmill structure.
Cloning and characterization of a cDNA coding for the lipoprotein-associated coagulation inhibitor shows that it consists of three tandem Kunitz-type inhibitory domains.

Abstract Human plasma contains a lipoprotein-associated coagulation inhibitor (LACI) which inactivates factor Xa directly, and in a Xa-dependent fashion also inhibits the VIIa-tissue factor complex of the extrinsic coagulation pathway. Rabbit polyclonal anti-LACI antiserum was used to screen human placental and fetal liver lambda gt11 cDNA libraries for the expression of LACI antigens. Immunologically positive clones were further tested for their ability to bind 125I-factor Xa. Seven clones were obtained which are immunologically and functionally active. The longest cDNA insert (lambda P9) of these isolates is 1.4 kilobases (kb) while other clones are 1.0 kb in length. Nucleotide sequence analysis shows that lambda P9 consists of 1431 bases that include a 5'-noncoding sequence of 132 nucleotides, an open reading frame of 912 nucleotides, and a 3'-noncoding region of 387 nucleotides. The open reading frame encodes a signal peptide of 28 residues followed by a 32-kilodalton protein of 276 residues. The predicted sequence of mature LACI contains 18 cysteines and three potential N-linked glycosylation sites. The amino acid sequence analysis of purified LACI's NH2 terminus and two of its proteolytic fragments match exactly those deduced from the cDNA sequence, indicating that the cDNA codes for LACI. The translated amino acid sequence of LACI shows several discernible domains, including a highly negatively charged NH2 terminus, three tandem Kunitz-type inhibitory domains, and a highly positively charged carboxyl terminus. Northern blot analysis shows that the following liver-derived cell lines, Chang liver, HepG2 hepatoma, and SK hepatoma all, contain two major species of mRNA (1.4 and 4.4 kb) which hybridize with LACI cDNA.
Endobronchial Valves for Challenging Air Leaks

Background Prolonged air leaks may result in increased morbidity and mortality. Endobronchial valves have been used as a nonoperative treatment. We evaluated the efficacy of endobronchial valves at achieving chest tube removal and hospital discharge for air leaks resulting from varied etiologies. Methods All consecutive patients undergoing endobronchial valve placement for persistent air leak were evaluated by a multidisciplinary team at a single institution. Those receiving valves underwent bronchoscopy with balloon occlusion to identify airways contributing to the leak. After airway sizing, unidirectional endobronchial valves were deployed. Results During an 18-month period, 21 patients underwent 24 valve placement procedures; 88 valves were placed (median, 3; mean, 3.6; range, 1 to 12). Patient age range was 16 months to 70 years. The underlying cause of persistent air leak was postoperative (n = 8), pneumothorax (n = 11), cavitary lung infection (n = 3), and postpneumonectomy bronchopleural fistula (n = 2). There were no valve-related complications during placement, dwell time, or removal. Three patients died as a result of their underlying disease, unrelated to valves. Of those with chest tubes who survived and were discharged, all had successful removal of their chest tubes. Median duration to chest tube removal after initial valve placement was 15 days (mean, 21 days; range, 0 to 86 days). Median length of stay after final valve placement was 5 days (mean, 15 days; range, 0 to 196 days). Conclusions Challenging air leaks often occur in medically compromised patients. They may persist despite multiple interventions. Endobronchial valves offer minimally invasive management. Time to chest tube removal and length of stay are variable, frequently because of clinical status and underlying disease.
Sperm morphology as diagnosed by strict criteria: probing the impact of teratozoospermia on fertilization rate and pregnancy outcome in a large in vitro fertilization population.

Objective To investigate the predictive value of sperm morphology assessed by strict criteria on IVF outcome. Design Retrospective analysis of all IVF cycles (January 1987 to December 1992). Main Outcome Measures All patients were assigned to one of three groups based on sperm morphology: P-pattern ( 14% normal forms). Morphology pattern was related to other semen characteristics and IVF outcome. Results Despite corrective measures at oocyte insemination, the fertilization rate was significantly different among the three morphology groups, P Conclusions Strict morphology is an excellent biomarker of sperm fertilizing capacity, independent of motility and concentration. P-pattern sperm may denote a poorer prognosis for establishing a pregnancy, even after a satisfactory fertilization rate is achieved.
RFLP map of soybean

The soybean is one of the oldest cultivated crops. It first emerged as a domesticated plant around the 11th century B.C. (Hymowitz 1970), although references to soybean appear in books written over 4500 years ago (Smith and Huyser 1987). The soybean was first planted in the United States in Thunderbolt, GA, in 1765 (Hymowitz and Harlan 1983). It was originally planted as a forage crop but by the early 1900’s became of interest as an oilseed crop (Smith and Huyser 1987), an interest that continues today.
Mutual Fund Share Classes and Broker Incentives

U.S. SEC Rule 18f-3 allows mutual funds to offer multiple share classes that represent claims on the same underlying assets. Share classes differ with respect to distribution arrangements, which are modified by varying the timing and magnitude of load charges and annual distribution fees. For investors, the choice of share classes depends primarily on the expected holding period. Rule 18f-3 has also given rise to broker compensation arrangements that differ among share classes and, consequently, create for brokers a stake in the class of shares clients purchase. In most circumstances and for most share class structures, brokers have monetary incentives to sell the class of shares that is least advantageous to investors. This conflict of interest is especially troubling because of the probable lack of financial sophistication of investors who pay for investment advice about mutual funds. The adverse incentives are potentially damaging to the mutual fund industry and should provoke a reconsideration of mult...
Cowpox virus evades CTL recognition and inhibits the intracellular transport of MHC class I molecules

Orthopoxviruses evade host immune responses by using a number of strategies, including decoy chemokine receptors, regulation of apoptosis, and evasion of complement-mediated lysis. Different from other poxviral subfamilies, however, orthopoxviruses are not known to evade recognition by CTL. In fact, vaccinia virus (VV) is used as a vaccine against smallpox and a vector for eliciting strong T cell responses to foreign Ags. and both human and mouse T cells are readily stimulated by VV-infected APC in vitro. Surprisingly, however, CD8(+) T cells of mice infected with cowpox virus (CPV) or VV recognized APC infected with VV but not APC infected with CPV. Likewise, CD8(+) T cells from vaccinated human subjects could not be activated by CPV-infected targets and CPV prevented the recognition of VV-infected APC upon coinfection. Because CD8(+) T cells recognize viral peptides presented by MHC class I (MHC I), we examined surface expression, total levels, and intracellular maturation of MHC I in CPV- and VV-infected human and mouse cells. Although total levels of MHC I were unchanged, CPV reduced surface levels and inhibited the intracellular transport of MHC I early during infection. CPV did not prevent peptide loading of MHC I but completely inhibited MHC I exit from the endoplasmic reticulum. Because this inhibition was independent of viral replication, we conclude that an early gene product of CPV abrogates MHC I trafficking, thus rendering CPV-infected cells "invisible" to T cells. The absence of this immune evasion mechanism in VV likely limits virulence without compromising immunogenicity.
The Mobile Camera: Bodies, Anthropologists, and the Victorian Optic

The art historian Tamar Garb recently wrote, “It's hard to think of nineteenth-century visual practices without thinking of photography” (Garb 13).1 Likewise, it's surely hard to think of nineteent...
Pharmacological Treatment of Addiction: Normalization of Physiology and AIDS Risk Reduction

In the United States, it is estimated that over 2 million persons have used heroin at some time and between 500.000 and 1 million are heroin addicts. It is estimated that over 23 million have used cocaine at some time and, of those, between 600.000 and 900.000 use cocaine regularly and are cocaine addicts. Parenteral drug abuse has become the leading risk for development of HIV infection in many regions. Illicit use of other drugs may also contribute to increase risk for HIV infection. The goals of treatment for any addiction must include prevention of abstinence or withdrawal symptoms, reduction or elimination of “drug hunger” or craving and relapse, and normalization of physiological functions which have been disrupted by abuse of the drug. Long-term studies of the physiological effects, in addiction to studies of the safety and efficacy of the long-acting opioid methadone as used in the maintenance treatment of addiction, have shown that this drug successfully addresses each of these three goals. It is assumed that future studies will show that another long-acting opioid, L-alpha-acethyl methadol (LAAM), will have similar desirable effects.