cssi/SciSciGPT-SciSciNet huggingface dataset:
FILTERED VIOLENCE: PROPAGANDA MODEL AND POLITICAL ECONOMY OF THE INDIAN FILM INDUSTRY

Production, distribution, and consumption of cinematic violence raises several questions of academic import. Despite a plethora of research studies exploring the nature of screen violence and its effects on viewers, a serious debate on the influence of state machinery on the production of sanitized violence in movies is still wanting. Likewise, Bollywood’s role in advancing the Indian government’s agenda in war and peace times has been paid petite attention in academic discourses dealing with media-state interconnection. This article explores the relevance of Herman and Chomsky’s propaganda model as a framework for analysis and analyzes Bollywood’s movies based on stories of violence in war and peace times. The article discusses the connections with the Indian state apparatus that influences production processes in the Indian film industry by providing financial assistance and applying multifarious political, social, economic, and ideological pressures (filters). The findings suggest that the Bollywood movies support diplomatic initiatives of the Indian government through cinematic narratives of
The Arab Spring Uncoiled

If this special issue on Middle East protest had been published two years ago, it probably would have focused more on accounting for the failure of opposition movements than accountting for their successes. Since the "Arab Spring" emerged in the winter of 2011, however, observers have rushed to explain mass revolts in the region. This introduction to the special issue reviews some of the explanations offered for these extraordinary events, and finds that the factors that are frequently cited in these explanations do not map comfortably onto the sites of greatest protest in the region. The essay then suggests an alternative approach, one that looks past causation in an attempt to understand the lived experience of the uprisings. The goal is to examine how actors changed as they perceived the possibility of protest, how they made meaning of their lives through the act of protesting, or not protesting, during moments of exceptional confusion and stress. This approach focuses on the twists of history that con...
Influence of optical and interaction-induced dephasing effects on the short-pulse ionization of atomic gases

The ionization dynamics of dilute atomic gases induced by ultra-short high-intensity optical-pulse excitation is treated fully microscopically. The optical excitation is self-consistently coupled to the many-body interactions of the electrons, including their interactions with free electrons, ions, and neutral atoms. The theory is numerically evaluated for the example of a gas of hydrogen atoms for a broad range of pulses covering the tunnel ionization, multi-photon ionization, as well as the one-photon ionization regimes. It is shown that the many-body effects during the excitation distinctly influence the atomic ionization dynamics. The ionization degree after the pulse is dominated by the dephasing caused by the excitation-dependent interplay between the purely optical processes and the many-body interactions.
"Edadismo" en Brasil: ¿qué significa? ¿quién lo ejerce? ¿qué se puede hacer?

El objetivo principal de este articulo es llamar la atencion sobre el edadismo y la edad como parte de un sistema de prejuicio y discriminacion en Brasil. A pesar de que el edadismo y la discriminacion por edad sean terminos frecuentemente usados como sinonimos, el edadismo se refiere esencialmente a las actitudes que los individuos y la sociedad tiene frecuentemente con los demas en funcion de la edad, mientras que la discriminacion por edad describe un contexto en el que la edad es el factor decisivo. Un ejemplo de discriminacion por edad es un empleador que decide contratar, promocionar, reciclar o jubilar/prescindir de un funcionario en base solo a la edad. Pese a que fijarse en la edad de un individuo no sea inherentemente ofensivo, actuar por estereotipos basados en la edad es claramente un prejuicio contra el individuo, que muy a menudo no es rebatido por la sociedad. El presente articulo se basa en hallazgos empiricos y en el conocimiento acumulado sobre la discriminacion al anciano, ademas de discutir las posiciones teoricas que relacionan la discriminacion por franja de edad al edadismo. Defendemos que el edadismo, como practica de discriminacion por edad en Brasil, debe ser visto como parte de las multiples formas de discriminacion sufridas por los individuos. La premisa central que orienta este trabajo es que la forma en la que encuadremos el edadismo y las relaciones intergeneracionales tiene un efecto significativo, tanto en la discriminacion basada en la percepcion de la edad, como en el apoyo a programas sociales especificos por edad. Ilustraremos mientras describimos el caso de Brasil.
Architecture and technology issues for optical interconnects at the chip level

Potential optical interconnect solutions to future intra-chip communications bottlenecks are reviewed. The discussion focuses on key performance trade-offs in optical fabric concepts that replace the longest (upper layer) metal interconnects with fixed arbitrarily routed optical links to overcome the overall latency limits.
Mail Surveys and Response Rates: A Literature Review:

A review of empirical studies concerned with increasing response rates to mail questionnaires reveals the limited evidence upon which most widely accepted techniques are based. The only techniques ...
Timing and heritability of theNasobemia transformation inDrosophila.

Nasobemia (Ns) is a dominant homeotic mutant ofDrosophila melanogaster which converts parts or all of the antenna to mesothoracic leg.Ns has a temperature sensitive period between 48 and 60 h. The hypothesis thatNs acts during this period and is not required thereafter to maintain the homeotic transformation to leg was tested by removingNs fromNs/+ cells at different stages of development through X-ray induced somatic recombination. The expression of theNs homeotic transformation in recombinant wild type (+/+) cells increased sharply between 48 and 65 h. In clones induced after 65 h the expression of the leg transformation was equal in large and small +/+ clones. We interpret these results as supporting the hypothesis that transient action ofNs between 48 and 65 h switches antennal cells to a clonally stable leg determined state whose maintenance does not require futherNs action.
Assessing redox properties of standard humic substances

Redox properties of humic substances (HS) control important biogeochemical processes. Thus, accurate estimation of redox properties of HS is essential. However, there is no general consensus regarding the best available measurement method of HS redox properties. In this study, we compared several common HS redox property measurement methods using anthraquinone-2,6-disulfonate (AQDS) as model compound, and standard Elliot soil humic acid (1S102H, ESHA), reference Pahokee peat (1R103H, PPHA), and Suwannee River natural organic matter (1R101N, SRNOM) as representative HS. We found that the H2/Pd reduction method followed by incubation with ferric citrate (FeCit) reagent was incomplete, and the H2/Pd reduction method followed by incubation with potassium ferricyanide (K3Fe(CN)6) was insensitive. Stannous chloride (SnCl2) reduction followed by titration of excess stannous (Sn2+) by potassium dichromate (K2Cr2O7) was found to be most accurate. These findings will help in future investigations on detailed characterizations of functional groups of HS responsible for oxidation/reduction reactions.
Adoption of robot-assisted surgery and its impact on treatment patterns for newly diagnosed localized prostate cancer.

6513 Background: With the rapid increase of robotic surgical systems in hospitals, it is important to understand the impact on treatment patterns for localized prostate cancer. The objective of thi...
Aortic arch compliance and idiopathic unilateral vocal fold paralysis

Unilateral vocal fold paralysis results from impaired function of the recurrent laryngeal nerve (RLN) impacting breathing, swallowing, and voice production. A large proportion of adults suffering f...
Drs. Sheth and Aggarwal reply.

To the Editor: We were delighted to read the letter by Thakran, et al 1 and learn of the different interventions toward the same goals. It is impressive that the use of specialist rheumatology nurses improved the vaccination rate to 52%, which is similar to our results of 51.7%2. Specialist nurses can be helpful in clinical rheumatology practice. In general, we agree with Thakran, et al 1 regarding the risk of developing herpes zoster (HZ) with medications and their intervention of intense counseling, clarifying misconceptions, and emphasizing the importance of HZ vaccine by a specialty nurse. Such interventions are effective, but not sustainable or affordable to … Address correspondence to Dr. H. Sheth, University of Pittsburgh, Medicine, 3504 Fifth Ave., Suite 200, Pittsburgh, Pennsylvania 15217, USA. E-mail: hss2{at}pitt.edu
Cholinesterase Activity in Patients with Rheumatoid Arthritis

The changes in cholinesterase activity in whole blood (WB), plasma (P), and red blood cells (RBC) of 43 patients with rheumatoid arthritis were compared with these same values in 44 normal individuals. In the normal individuals the mean values and the standard deviations were: 127 ± 19 for WB, 99 ± 16 for P, and 165 ± 29 units for RBC, whereas in the patients with rheumatoid arthritis the values were 135 ± 32 for WB, 86 ± 19 for P, and 216 ± 65 units for RBC. Although the mean RBC values in patients were higher, significant specific variations from the normal, particularly those in whole blood and plasma, were not readily apparent. Therefore, the ratio (RBC:P) between cholinesterase activities of the two blood components were calculated and considered to be a much more sensitive approach in evaluating the pathologic process. The mean ratio in patients was 2.50 ± 0.70:1, compared with a mean ratio of 1.65 ± 0.29:1 for normal individuals. The RBC:P cholinesterase activity ratios of 36 of the 43 patients differed from the mean value for normal individuals by one standard deviation or more. These ratios increased with the severity of the disease.
Decreased class size, increased active learning? Intended and enacted teaching strategies in smaller classes:

Small class size is often used as an indicator of quality in higher education, and some research suggests that instructors in smaller classes more often use activities that are learner-centered and...
The accelerating pace of star formation

We study the temporal and spatial distribution of star formation rates in four well-studied star-forming regions in local molecular clouds(MCs): Taurus, Perseus, $\rho$ Ophiuchi, and Orion A. Using published mass and age estimates for young stellar objects in each system, we show that the rate of star formation over the last 10 Myrs has been accelerating and is (roughly) consistent with a $t^2$ power law. This is in line with previous studies of the star formation history of molecular clouds and with recent theoretical studies. We further study the clustering of star formation in the Orion Nebula Cluster(ONC). We examine the distribution of young stellar objects as a function of their age by computing an effective half-light radius for these young stars subdivided into age bins. We show that the distribution of young stellar objects is broadly consistent with the star formation being entirely localized within the central region. We also find a slow radial expansion of the newly formed stars at a velocity of $v=0.17\,{\rm km\,s}^{-1}$, which is roughly the sound speed of the cold molecular gas. This strongly suggests the dense structures that form stars persist much longer than the local dynamical time. We argue that this structure is quasi-static in nature and is likely the result of the density profile approaching an attractor solution as suggested by recent analytic and numerical analysis.
SOUTH ASIA AS A SEMANTIC AREA: Forms, Meanings and Their Connections

(1982). SOUTH ASIA AS A SEMANTIC AREA: Forms, Meanings and Their Connections. South Asian Review: Vol. 6, No. 3, pp. 30-41.
Date of sowing and emergence timing affect growth and development of loblolly pine seedlings

Loblolly pine (Pinus taeda L.) seeds were sown from February to June in Alabama, U.S.A. If sowing was conducted in May or June, seedling emergence was reduced and seedling mortality increased. Seedlings from earlier sowings grew to greater sizes, but seedlings from later sowings grew later into the fall. Within any given sowing date, the earliest seedlings to emerge grew largest. Seedlings from the February sowing formed buds in mid-summer, flushed, and in some instances flushed yet again. However, by early October, not all seedlings from May and June sowings had formed an initial bud.
Stereo Thermal Marking Velocimetry

This paper presents a novel approach to measuring and mapping shape and motion of the water surface. The approach combines and borrows from existing techniques, such as stereo imaging shape recognition and tracking, infrared laser marking and thermography, and particle image velocimetry. The system consists of a high power infrared laser beam controlled by a programmable marking head and two infrared cameras tracking the thermal pattern projected by the beam onto the water surface. The paper provides detailed description of the setup, discusses the choice of the thermal pattern, and describes the infrared image processing algorithm. An example of resolved surface shape and velocity maps is given for an experiment conducted in a laboratory wave tank.
Cell-subtype-specific changes in adenosine pathways in schizophrenia

Prior work in animal models implicates abnormalities of adenosine metabolism in astrocytes as a possible pathophysiological mechanism underlying the symptoms of schizophrenia. In the present study, we sought to reverse-translate these findings back to the human brain in schizophrenia, focusing on the following questions: (1) Which components of the adenosine system are dysregulated in schizophrenia, and (2) are these changes limited to astrocytes? To address these questions, we captured enriched populations of DLPFC pyramidal neurons and astrocytes from schizophrenia and control subjects using laser capture microdissection and assessed expression of adenosine system components using qPCR. Interestingly, we found changes in enriched populations of astrocytes and neurons spanning metabolic and catabolic pathways. Ectonucleoside triphosphate diphosphohydrolase-1 (ENTPD1) and ENTPD2 mRNA levels were significantly decreased (p < 0.05, n = 16 per group) in enriched populations of astrocytes; in pyramidal neurons equilibrative nucleoside transporter 1 (ENT1) and adenosine A1 receptor mRNA levels were significantly decreased, with an increase in adenosine deaminase (ADA) (p < 0.05, n = 16 per group). Rodent studies suggest that some of our findings (A1R and ENTPD2) may be due to treatment with antipsychotics. Our findings suggest changes in expression of genes involved in regulating metabolism of ATP in enriched populations of astrocytes, leading to lower availability of substrates needed to generate adenosine. In pyramidal neurons, changes in ENT1 and ADA mRNA may suggest increased catabolism of adenosine. These results offer new insights into the cell-subtype-specific pathophysiology of the adenosine system in this illness.
Biogeographic origins of Darwin's finches (Thraupidae: Coerebinae)

ABSTRACT Darwin's finches are considered a classic example of an adaptive radiation, and have been the focus of numerous studies from ecological and evolutionary perspectives. Few studies, however, have attempted to investigate the biogeographic origins of Darwin's finches. In this paper, we reconstruct the ancestral biogeography of Coerebinae, the tanager subfamily that contains Darwin's finches and their 14 closest relatives. We use this reconstruction to examine the origin of Darwin's finches, and the diversification of this clade of tanagers. We test multiple biogeographic models using the R package BioGeoBEARS utilizing a recent multilocus phylogeny. We used these models to examine 2 different hypotheses regarding the biogeographic origin of Darwin's finches. The majority of ancestral ranges within this subfamily were estimated as Caribbean restricted. Biogeographic models run using 8 regions suggest Darwin's finches arose from a long-distance dispersal event from the Caribbean Islands as opposed to ...
Spontaneous Tax Coordination: On Adopting a Comparative Approach to Reforming the U.S. International Tax Regime

Despite being widely-acknowledged as an important tax policy goal, simplification of the U.S. international tax regime has received little substantive attention from commentators. When simplicity concerns have been addressed, commentators have generally considered only the internal complexity produced by individual U.S. rules or by the interaction of one U.S. rule with another U.S. rule. In practice, however, the U.S. international tax regime does not operate in isolation, but rather continuously interacts with other countries' international tax regimes. These interactions often engender conflicts that produce additional, external complexity. As a result, true simplification of the U.S. international tax regime can be achieved only when the problem of complexity is viewed from a holistic perspective that takes into account both the regime's internal and external complexity. With the need for a holistic approach in mind, this article explores the viability of adopting tax coordination - pursued through the use of comparative law as an aid to legislation - as a framework within which the U.S. international tax regime might be reformed. Initially, the concepts of tax coordination and tax harmonization are refined to provide a working vocabulary for use in the remainder of the article. Next, the manner in which the proposed framework is expected to operate in theory is detailed and the costs and benefits of adopting the proposed framework are considered. Finally, the manner in which the proposed framework is expected to operate in practice is examined using reform of the provisions governing the treatment of cross-border charitable contributions as an example.
AlGaAs as a Dielectric on GaAs for Digital I.C.’s: Problems and Solutions

GaAs field effect transistors (FETs) offer significant speed advantage over FBI’s based on Si because the electrons are inherently faster in GaAs. Field effect transistors based on the AlGaAs/GaAs heterostructure have demonstrated unity current gain cut-off frequencies (fT) in excess of 110 GHz. Switching times of 5.8 ps have been measured in ring oscillator circuits cooled to 77 K. The presence of an intrinsic AlGaAs defect, DX, however, results in behavior which is undesirable for FET operation, particularly in digital applications. This defect is observed in all n-type AlGaAs and appears to be as dense as the doping concentration, itself. There are several solutions to the problems caused by the DX centers in doped AlGaAs. By using self-aligned technologies, it is possible to use undoped AlGaAs which does not contain the DX center. Modifications such as the use of a thin InGaAs layer at the heterointerface with lower Al mole fraction AlGaAs allow us to use more standard GaAs FET technology and still avoid most of the problems associated with the DX center. These solutions to the problems of traps in AlGaAs may allow us not to rule out AlGaAs as a reliable dielectric for GaAs transistor applications.
Innocent Heart Murmurs

Innocent heart murmurs are encountered in 50% of all children. Innocent heart murmurs are not associated with any other cardiac symptoms of signs which may indicate cardiac pathology. Innocent heart murmurs are systolic and may be continuous in the case of venous hum, but never purely diastolic in nature. Typical innocent heart murmurs are 1–2/6 and never more than 3/6 in intensity. If the child is cooperative, it is essential to evaluate the change in intensity of heart murmurs through maneuvers that decrease cardiac pre-load such as moving the child from supine to sitting to standing positions and with Valsalva maneuver. Children with innocent heart murmurs should have normal findings on ECG and cheat X-ray.
Genome wide association and gene enrichment analysis reveal membrane anchoring and structural proteins associated with meat quality in beef

Meat quality related phenotypes are difficult and expensive to measure and predict but are ideal candidates for genomic selection if genetic markers that account for a worthwhile proportion of the phenotypic variation can be identified. The objectives of this study were: 1) to perform genome wide association analyses for Warner-Bratzler Shear Force (WBSF), marbling, cooking loss, tenderness, juiciness, connective tissue and flavor; 2) to determine enriched pathways present in each genome wide association analysis; and 3) to identify potential candidate genes with multiple quantitative trait loci (QTL) associated with meat quality. The WBSF, marbling and cooking loss traits were measured in longissimus dorsi muscle from 672 steers. Out of these, 495 animals were used to measure tenderness, juiciness, connective tissue and flavor by a sensory panel. All animals were genotyped for 221,077 markers and included in a genome wide association analysis. A total number of 68 genomic regions covering 52 genes were identified using the whole genome association approach; 48% of these genes encode transmembrane proteins or membrane associated molecules. Two enrichment analysis were performed: a tissue restricted gene enrichment applying a correlation analysis between raw associated single nucleotide polymorphisms (SNPs) by trait, and a functional classification analysis performed using the DAVID Bioinformatic Resources 6.8 server. The tissue restricted gene enrichment approach identified eleven pathways including “Endoplasmic reticulum membrane” that influenced multiple traits simultaneously. The DAVID functional classification analysis uncovered eleven clusters related to transmembrane or structural proteins. A gene network was constructed where the number of raw associated uncorrelated SNPs for each gene across all traits was used as a weight. A multiple SNP association analysis was performed for the top five most connected genes in the gene-trait network. The gene network identified the EVC2, ANXA10 and PKHD1 genes as potentially harboring multiple QTLs. Polymorphisms identified in structural proteins can modulate two different processes with direct effect on meat quality: in vivo myocyte cytoskeletal organization and postmortem proteolysis. The main result from the present analysis is the uncovering of several candidate genes associated with meat quality that have structural function in the skeletal muscle.
30-day Outcomes in Primary vs. Revision Posterior Spinal Fusion for Pediatric Spinal Deformity

Abstract Objectives Current evidence, with regard to primary vs. revision spinal fusions in pediatric spine deformities, is limited to inpatient outcomes only. The current study aims to analyze and compare 30-day outcomes in pediatric spine deformity patients undergoing a primary vs. a revision posterior spinal fusion. Patients and methods The 2012–2016 American College of Surgeons – National Surgical Quality Improvement Program (ACS-NSQIP) Pediatric database was queried using Current Procedural Terminology (CPT) codes for patients undergoing posterior spinal fusions (22800, 22802 and 22804). Patients undergoing concurrent anterior fusion/combined fusion and anterior-only fusions were removed from the study. Revision spinal fusions were captured using CPT codes for re-insertion of spinal fixation device (22830), exploration of spinal fusions (22849), 22850 and 22852 (removal of posterior instrumentation). Results Out of a total of 13,398 patients, 332 (2.5%) underwent a revision posterior spinal fusion and the remained underwent primary spinal fusion. Following adjustment for baseline clinical characteristics, patients undergoing revision posterior spinal fusions were at a higher risk of deep surgical site infections (OR 2.43 [95% CI 1.10–5.35]; p = 0.028), organ/space surgical site infections (OR 4.09 [1.19–14.04]; p = 0.025) and 30-day unplanned re-operations (OR 1.87 [95% CI 1.17–3.00]. Conclusions Pediatric spine deformity patients undergoing revision spinal fusions are at a higher risk of experiencing wound-complications and subsequent unplanned re-operations within 30-days of surgery. Providers should promote careful wound-care and/or awareness among care-givers to minimize the risks and costs associated with these specific adverse outcomes.
U.S. National 90-Day Readmissions After Opioid Overdose Discharge.

Introduction U.S. hospital discharges for opioid overdose increased substantially during the past two decades. This brief report describes 90-day readmissions among patients discharged from inpatient stays for opioid overdose. Methods In 2018, survey-weighted analysis of hospital stays in the 2016 Healthcare Cost and Utilization Project National Readmissions Database yielded the national estimated proportion of patients with opioid overdose stays that had all-cause readmissions within ≤90 days. A multivariable logistic regression model assessed index stay factors associated with readmission by type (opioid overdose or not). Number of readmissions per patient was assessed. Results More than 24% (n=14,351/58,850) of patients with non-fatal index stays for opioid overdose had at least one all-cause readmission ≤90 days of index stay discharge and 3% (n=1,658/58,850) of patients had at least one opioid overdose readmission. Less than 0.2% (n=104/58,850) of patients had more than one readmission for opioid overdose. Patient demographic characteristics (e.g., male, older age), comorbidities diagnosed during the index stay (e.g., drug use disorder, chronic pulmonary disease, psychoses), and other index stay factors (Medicare or Medicaid primary payer, discharge against medical advice) were significantly associated with both opioid overdose and non-opioid overdose readmissions. Nearly 30% of index stays for opioid overdose included heroin, which was significantly associated with opioid overdose readmissions. Conclusions A quarter of opioid overdose patients have ≤90 days all-cause readmissions, although opioid overdose readmission is uncommon. Effective strategies to reduce readmissions will address substance use disorder as well as comorbid physical and mental health conditions.
A Flare-up of Systemic Lupus Erythematosus with Unusual Enteric Predominance

Enteritis associated with systemic lupus erythematosus (SLE) is a rare and unusual manifestation of the gastrointestinal (GI) consequences of SLE itself. Complications of the enteritis component include mesenteric vasculitis, intestinal pseudo-obstruction, and protein-losing enteropathy. Lupus enteritis is very responsive to treatment with pulse steroids in almost 70% of the patients, but it is critical to diagnose it early to prevent devastating organ damage. The case describes a 21-year-old Caucasian female with a past medical history of uncomplicated laparoscopic appendectomy (one month prior to the time of presentation), major depressive disorder, asthma, iron deficiency anemia, pelvic inflammatory disease secondary to sexually transmitted Chlamydia trachomatis infection, and SLE (diagnosed two weeks prior to presentation). She had been transferred from an outside facility with complaints of severe right upper quadrant (RUQ) abdominal pain for one day. The patient had run out of her prescription for steroids and hydroxychloroquine two days prior to the presentation. Her abdominal pain was accompanied by nausea, bilious vomiting, non-bloody diarrhea, a photosensitive facial rash, left-sided pressure-type periorbital headache, diplopia, oral ulcers, inappetence, joint stiffness, and muscle weakness. A CT of the abdomen and pelvis from an outside facility showed enteritis involving the proximal jejunum with associated mesenteric edema and ascites, suggesting infectious versus inflammatory or autoimmune etiology. A repeat CT scan a few days later confirmed these findings along with adjacent mesenteric fat stranding. Her autoimmune workup confirmed the serological diagnosis of SLE, and assessment of the SLE Disease Activity Index (SLEDAI) confirmed the diagnosis of a severe SLE flare. Upper endoscopy detected edematous mucosa in the duodenum and jejunum without active bleeding, gastropathy, or ulceration. No surgical intervention was required. Her symptoms resolved with supportive care, pulse steroids, and hydroxychloroquine. She was discharged with instructions for outpatient follow-up with gastroenterology and rheumatology.
Linking School Nurses With Health Care Systems Using EHRs: An Integrative Review:

School-aged children spend around 1,080 hr at school each year and many of them have chronic diseases; therefore, it is imperative to include school nurses as part of the health care team. Care coordination between health care providers and school nurses is currently hindered by communication that relies on an inadequate system of fax, phone, and traditional mail. Using electronic health records (EHRs) to link school nurses and health care systems is usually limited in scope despite EHRs advancement in these health care systems. No literature is currently available showing the number of hospitals and health care systems that provide EHR access to school nurses. The purpose of this article was to present a literature review on EHR access for school nurses nationally. This review along with the legal and logistical considerations for this type of implementation will be discussed.
A screen of FDA-approved drugs identifies inhibitors of Protein Tyrosine Phosphatase 4A3 (PTP4A3 or PRL-3)

ABSTRACT Protein tyrosine phosphatase 4A3 (PTP4A3 or PRL-3) is highly expressed in a variety of cancers, where it promotes tumor cell migration and metastasis leading to poor prognosis. Despite its clinical significance, there are currently no viable options to target PRL-3 in vivo. Here, we screened 1,443 FDA-approved drugs for their ability to inhibit the activity of the PRL phosphatase family. We identified five specific inhibitors for PRL-3 as well as one selective inhibitor of PRL-2. Additionally, we found nine drugs that broadly and significantly suppressed PRL activity. Two of these broad PRL inhibitors, Salirasib and Candesartan blocked PRL-3-induced migration in human embryonic kidney (HEK) cells with no negative impact on cell viability. Both drugs prevented migration of PRL-3 expressing human colorectal cancer cells to a similar degree as the research-grade PRL inhibitor, Thienopyridone, and are selective towards PRLs over other phosphatases. In silico modeling revealed that Salirasib binds a putative allosteric site near the WPD loop of PRL-3, while Candesartan binds a potentially novel targetable site adjacent to the CX5R motif. Inhibitor binding at either of these sites is predicted to trap PRL-3 in a closed conformation, preventing substrate binding and inhibiting function.
Abstract PR06: An in vivo KRAS allelic series reveals distinct phenotypes of common oncogenic variants

KRAS is the most frequently mutated oncogene in cancer. Tumor sequencing has revealed a complex spectrum of KRAS mutations across different cancer types, yet there is little understanding of how specific KRAS alterations impact tumor in initiation, progression, or therapy response. Using high-fidelity CRISPR-based engineering, we created an allelic series of new LSL-Kras mutant mice, reflecting codon 12 and 13 mutations that are highly prevalent in lung (KRASG12C), pancreas (KRASG12R), and colon (KRASG13D) cancers. Induction of each mutation in the developing mouse pancreas reveals striking quantitative and qualitative differences in the degree of ductal transformation and premalignant progression. Further, using organoid models we show that KRASG13D mutants respond to EGFR inhibition, while the antiproliferative effect of KRASG12C-selective inhibitors can be overcome by upstream EGFR signaling. Together, these new mouse strains provide an ideal method for investigating KRAS biology in vivo and for developing preclinical precision oncology models of KRAS-mutant pancreas, colon, and lung cancers. This abstract is also being presented as Poster A41. Citation Format: Maria Paz Zafra, Direna Alonso-Curbelo, Sukanya Goswami, Emma M Schatoff, Teng Han, John E. Wilkinson, Lukas E. Dow. An in vivo KRAS allelic series reveals distinct phenotypes of common oncogenic variants [abstract]. In: Proceedings of the AACR Special Conference on the Evolving Landscape of Cancer Modeling; 2020 Mar 2-5; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2020;80(11 Suppl):Abstract nr PR06.
Urine Biomarkers of Kidney Tubule Health and Incident CKD Stage 3 in Women Living With HIV: A Repeated Measures Study.

Rationale & Objective Single measurements of urinary biomarkers reflecting kidney tubule health are associated with chronic kidney disease (CKD) risk in HIV infection, but the prognostic value of repeat measurements over time is unknown. Study Design Cohort study. Setting & Participants 647 women living with HIV infection enrolled in the Women's Interagency Health Study. Exposures 14 urinary biomarkers of kidney tubule health measured at 2 visits over a 3-year period. Outcome Incident CKD, defined as estimated glomerular filtration rate (eGFR) Analytical Approach We used multivariable generalized estimating equations adjusting for CKD risk factors to evaluate baseline, time-updated, and change-over-time biomarker associations with incident CKD. We compared CKD discrimination between models with and without a parsimoniously selected set of biomarkers. Results During a median 7 years of follow-up, 9.7% (63/647) developed CKD. In multivariable-adjusted analyses, 3 of 14 baseline biomarkers associated with incident CKD. In contrast, 10 of 14 time-updated biomarkers and 9 of 14 biomarkers modeled as change over time associated with incident CKD. Urinary epidermal growth factor (EGF), α1-microglobulin (A1M), and albumin were selected using penalized regression methods. In the time-updated model, lower urinary EGF (risk ratio [RR] per 2-fold higher time-updated biomarker levels, 0.69; 95% CI, 0.58-0.81), higher urinary A1M (RR, 1.47; 95% CI, 1.25-1.73), and higher urinary albumin excretion (RR, 1.21; 95% CI, 1.03-1.42) were jointly associated with increased risk for CKD. Compared with a base model (C statistic, 0.75), CKD discrimination improved after adding urinary EGF, A1M, and albumin values across baseline (C=0.81), time-updated (C=0.83), and change-over-time (C=0.83) models (P Limitations Observational design, incident CKD definition limited to eGFR. Conclusions Repeat urinary biomarker measurements for kidney tubule health have stronger associations with incident CKD compared with baseline measurements and moderately improve CKD discrimination in women living with HIV infection.
Lunar Ion Flux and Energy

The dynamics of the lunar ionosphere and resulting flux of lunar ions to the lunar surface are reviewed. In the Lunar rest frame, ions formed from the neutral lunar atmosphere are accelerated by the interplanetary electric and magnetic fields. The trajectories of heavier ions are primarily along the electric field; the ion flux is in a direction perpendicular to the solar wind flow, correlated to the orientation of the interplanetary magnetic field, and impacts the surface with energies of tens of electron volts to a few keV. Thus we predict a relatively energetic (compared to thermal energies), highly directional, lunar ion flux but with the possibility that light ions such as hydrogen can execute orbits that return them to portions of the lunar surface not directly exposed to the solar wind. The effects of surface electric and magnetic fields are discussed, as is the ion energy spectrum. We calculate the trapping of atmospheric ions which impact the surface and from this the density of neutral Ar40 in the lunar atmosphere. We show that using the acceleration model, the lunar atmosphere total neutral number density can be calculated from ion detector data.
Wilcoxon's signed-rank statistic: what null hypothesis and why it matters

In statistical literature, the term 'signed-rank test' (or 'Wilcoxon signed-rank test') has been used to refer to two distinct tests: a test for symmetry of distribution and a test for the median of a symmetric distribution, sharing a common test statistic. To avoid potential ambiguity, we propose to refer to those two tests by different names, as 'test for symmetry based on signed-rank statistic' and 'test for median based on signed-rank statistic', respectively. The utility of such terminological differentiation should become evident through our discussion of how those tests connect and contrast with sign test and one-sample t-test. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.
The Role of Discourse Novelty in Early Word Learning

2 studies of word learning are reported. In Study 1, 24-month-old children and 2 adults played with 3 nameless objects. These objects were placed in a clear box along with a novel nameless object. The adults then displayed excitement about the contents of the box and modeled a new word. Comparison with a control condition indicated significant learning of the new word for the novel object. Study 2 followed the same procedure with one difference: the children played with the novel object while the adults were absent. Thus, at the time of the language model the target object was novel only to the adults, not to the children. Again subjects displayed significant learning of the new word. This last finding suggests that 24-month-old children understand that adults use language for things that are novel to the discourse context and that this novelty is determined from the speaker's point of view.
The roles of three palmitoylation sites of RPE65 in its membrane association and isomerohydrolase activity.

Purpose RPE65, a membrane-associated protein predominantly expressed in the retinal pigment epithelium, is the isomerohydrolase in the retinoid visual cycle. Three cysteine (Cys) residues, Cys231, Cys329, and Cys330, in RPE65 have been shown to be palmitoylated and have been suggested to be responsible for its membrane association. The purpose of this study was to define the role of these Cys residues in palmitoylation, membrane association, and isomerohydrolase activity of RPE65. Methods The three Cys residues in RPE65 were replaced by Alanine (Ala) with site-directed mutagenesis. The mutant protein levels and subcellular localizations were determined by Western blot analysis and subcellular fractionation, respectively. Their enzymatic activities were evaluated with the in vitro isomerohydrolase activity assay. Palmitoylation of the mutants was examined by labeling of the protein with [3H]-labeled palmitic acid. Results Mutation of any single residue of these three Cys significantly reduced protein levels of RPE65. Similar to wild-type RPE65, however, all three single Cys mutants were predominantly present in the membrane fraction. Mutations of any one or two of these Cys substantially weakened the isomerohydrolase activity of RPE65, whereas mutations of all three Cys (triple mutant) completely abolished the enzymatic activity. However, this triple Cys mutant was still palmitoylated and associated with the membrane, although at a reduced level. Conclusions There are additional yet to be identified palmitoylation sites in RPE65. The structural distortions induced by the Cys mutations may be responsible for the mislocalization and decreased isomerohydrolase activities of RPE65.
Thermodynamic methods for pressure relief system design parameters

Abstract The design of fire relief systems for petroleum refineries, petrochemical, chemical and natural gas plants requires two accurate system design parameters: the latent heat of vaporization and sonic velocity. These design parameters further require accurate thermodynamic properties. At present, various approximate methods and thermodynamic models are utilized to estimate the latent heat of vaporization of fluid mixtures with varying degrees of success. Similarly, approximate methods have been used in industry to estimate the sonic velocity at which compressible fluid mixtures can flow through relief valve orifices and discharge piping. This paper presents the following: 1. Thermodynamically rigorous methods for the calculation of the latent heat of vaporization and the sonic velocity . These methods are applied to typical fluid mixtures using industry-standard property models and compare the calculated results with data published in scientific literature. 2. The American Petroleum Institute (API) recommendation of the minimum value of latent heat of vaporization of hydrocarbon mixtures is too large to accept for safe fire relief system design when no accurate latent-heat value is available near the critical point . Note: recommendation by API for minimum approximate heat of vaporization of multicomponent hydrocarbon mixtures in the absence of latent-heat data at the critical point is 50 Btu/lb (116 kJ/kg) – see Section 3.15.3.1 of API Recommended Practice 521: “Guide for Pressure-Relieving and Depressuring Systems, 1997”). 3. The need of accurate thermodynamic property data of fluid mixtures necessary to validate the thermodynamic model at relief system operating conditions . Currently, these types of data are scarce in the open literature because data measurements have been difficult at the temperatures and pressure of interest.
Fluorescein angiography: Risks

Abstract Fluorescein angiography has become a very important diagnostic aid in ophthalmology. The principles, technique and interpretation are briefly discussed. The risks of fluorescein angiography include direct ones resulting from injection of the dye as well as possible retinal damage from light exposure during the procedure. Retinal irradiance levels from fluorescein angiography have been compared to retinal threshold levels in normal animal eyes and using conventional techniques, appear to be safe. Its safety, however, in patients with retinal or other ocular disorders is unknown and requires further investigation.
Aerodynamic analysis of the tektite problem

Abstract If a recently measured vapor pressure function of tektite material is used, trajectory and ablation analysis gives a band less than 2° wide, and adjacent to the skipping limit, for the entry angles of button-type australites. Problems of shape, distribution and atmospheric flight of tektites can be solved if tektites are assumed to have ablated from a hypothetical skipping parent body. In particular, this hypothesis explains the narrow range of shallow entry angles of australites. Aerodynamic evidence precludes terrestrial origin of tektites or tektite material.
Impact of transfusion policy on acute coronary syndrome after major vascular reconstruction.

Abstract Objectives To investigate the impact of a restrictive transfusion approach, as indicated by accepting a perioperative hemoglobin (Hb) level as low as 8 g/dL, on the incidence of acute coronary syndrome (ACS) and mortality after major vascular reconstruction. Methods Using a case-control design, 45 patients who underwent vascular reconstruction and developed postoperative ACS were compared with 135 patients treated with similar procedures who did not suffer ACS postoperatively. Results A history of CAD was more often present in the ACS group (16% vs 56%) and was an independent predictor of ACS (odds ratio [OR] = 6.62; confidence interval [CI], 3.16–13.88; P P = .001). Postoperative (Hb) levels as low as 8 g/dL were well tolerated and had no impact on the occurrence of ACS (OR = .61; CI, 0.29–1.26; P = .181) or death (OR = 1.33; CI, 0.52–3.43; P = .547). The presence of CAD for a given Hb level did not increase the odds of either ACS (OR = 3.43; CI, .75–15.6; P = .112) or death (OR = 2.02; CI, .5–19.55; P = .543). Conclusions A restrictive transfusion policy is justified in patients undergoing major vascular reconstruction, even in the presence of appropriately managed cad.
Cognitive Memory: Human Like Memory

Taking inspiration from life experience, the authors have devised a new form of computer memory. Certain conjectures about human memory are keys to the central idea. This paper presents a design of a practical and useful "cognitive" memory system in which the new memory does not function like a computer memory where specific data is stored in specific numbered registers; retrieval is done by reading the contents of the specified memory register, or done by matching key words as with a document search. Incoming sensory data would be stored at the next available empty memory location and could be stored redundantly at several empty locations. The stored sensory data would neither have key words nor would it be located in known or specified memory locations. Retrieval would be initiated by a prompt signal from a current set of sensory inputs or patterns. The search would be done by a retrieval system that makes use of auto-associative artificial neural networks. In this paper, the authors present a practical application of this cognitive memory system to human facial recognition.
Surgical Critical Care: Still at Risk?

It has been a great honor and privilege to serve as your president and to give this year's presidential address. Considering that this is the last Western Surgical Association presidential address to be given in the 1900s, it seems necessary to mention the rapidly approaching third millennium. With only a little more than 46 days left, I am not particularly excited about having to write a "00" whenever I date something. It just does not seem like a real date to me. I have, however, resisted the temptation to speculate on the 21st century, let alone the next millennium, largely because my crystal ball is no better than any of yours. When I began as a medical student in the mid 1950s, my wildest dreams could not have predicted what dramatic advances would occur in the last half of this century. At that time, the first cardiopulmonary bypass cases were being performed for valvular and congenital disease. Kidneys had only recently been transplanted in Paris, France, and Boston, Massachusetts. Plastic surgery had yet to do a free flap and video-guided endoscopic surgery was still decades away. Intensive care units (ICUs) were just opening up, but they were little more than places where frequent vital signs and reliable intake and outputs were obtained.
The effect of indirect myocardial revascularization on left ventricular function

Abstract The effect of indirect myocardial revascularization on left ventricular function was studied in the dog heart using a right heart pulmonary circulatory bypass preparation at periods of 3–7 months after ameroid constriction of the left anterior descending artery and double internal mammary artery implants. Implant flow in the working heart was less than 10 ml./minute in all but one animal and no measureable change in left ventricular function could be detected with occlusion of the implants. Left ventricular function in the implanted animals was significantly better than that in nonrevascularized animals, suggesting that, despite the small measureable implant flow observed in this experimental preparation, indirect revascularization apparently improved intercoronary collateral circulation or distribution of myocardial blood flow in the ischemic heart.