cssi/SciSciGPT-SciSciNet huggingface dataset:
Analysis of the epidemiological characteristics of measles in the Zhabei district, Shanghai from 1999 to 2008.

Objective To ascertain the epidemiological characteristics of measles in the Zhabei district of Shanghai and provide evidence for specific strategies and measures for measles prevention and control.Methods Descriptive analysis was performed on data on measles in the Zhabei district from 1999 to 2008.Results One hundred and eighty-five cases were reported in the entire Zhabei district from 1999 to 2008,and no deaths were reported.The average morbidity in the Zhabei district was 2.31/100 000.Measles incidence in the migrant population was 16.11 times higher than in the native population.The peak season was from March to August,in which 78.92% of cases appeared.The male-to-female ratio of patients was 1.08∶1.Children 10 years of age accounted for 51.89% of cases and those ≥20 years of age accounted for 37.84%,representing the majority of patients.Cases involving local habitants mostly consisted of adults and morbidity was highest in individuals ≥20 years of age(56.14%).Cases involving the migrant population mostly consisted of children and the age of morbidity peaked for children 10 years of age(58.59%).Of all of the patients,56.76% had no history of measles immunization while the inoculation history of 28.65% was unknown.Conclusion Action should be taken to enhance the immunization of the migrant population.Provinces should administer the measles vaccine in a timely manner and increase the rate of two-dose measles vaccination.Measles surveillance should also be emphasized and the range of measles immunization should be expanded to adults.
Potential Interaction between Clarithromycin and Warfarin

ObjectiveTo report a possible drug interaction between clarithromycin and warfarin in a patient with chronic atrial fibrillation.Case SummaryA patient with chronic atrial fibrillation was placed on...
Granulosa cell pyknosis in the dominant follicle of monkeys

One of the primary morphologic criteria used as the first sign of degeneration of an antral follicle is the presence of a pyknotic nucleus in granulosa cells lining the lumen. This study was undertaken to determine whether granulosa cells with a pyknotic nucleus are also present in the putative dominant follicle. Dominance was verified by elevations of estradiol either following luteectomy or during the later stages of the follicular phase of the menstrual cycle. Some pyknosis is normal even in the viable dominant follicle at cycle day 8 or 12. Therefore, when evaluating the morphologic status of a follicle, one should examine several areas to assure proper evaluation.
Every Line in a Euclidean Plane Is an Ordered Field (OF)

This chapter is concerned with an arbitrary line in a Euclidean plane. It uses translations to define an operation of addition, and dilations to define multiplication on such a line; when equipped with these operations, the line becomes a field (defined in Chapter 1 Section 1.5). An ordering of the line is defined, so that the line becomes an ordered field. These concepts are used to define distance between points, and the length of a segment.
Apical Membrane Permeability of Mytilus Gill: Influence of Ultrastructure, Salinity and Competitive Inhibitors on Amino Acid Fluxes

The apical membrane of gill integumental cells from the mussels Mytilus edulis and M. californianus serves as a permeability barrier separating sea water from a cytoplasm rich in amino acids and other small organic molecules. Morphometric analysis of transmission electronmicrographs indicates that the membrane area of these cells is increased between 10- and 18-fold by the presence of a microvillous brush border. The microvilli do not appear to influence the kinetics of solute transport across the cell apex, as determined using a mathematical model of the relationship between membrane structure and the kinetics of transport. Rates of amino acid loss from the integument were low, and estimates of the upper limit of the passive permeability of the apical membrane to amino acids ranged from 0.5 to 10×10−10 cm s−1. Abrupt exposure of intact mussels or isolated gill tissue to 60% sea water (19% salinity) resulted in a transient, 40- to 80-fold increase in the rate of loss of all amino acids from integumental tissues. Upon exposure to full-strength sea water, efflux rates returned to near control values. Exposure to 60% sea water also inhibited the carrier-mediated accumulation of amino acid: uptake of 0.5 μmol1−1 [14C]alanine and [14C]taurine was reduced by 80% compared to control uptake in 100% sea water. This inhibition was not adequate to account for the increase in net efflux of taurine from gill tissue into 60% artificial sea water (ASW), though the inhibition of alanine uptake may have contributed significantly to the increased loss of this amino acid. Efflux of discrete structural classes of amino acid occurred when integumental tissues were exposed to 50 μmoll−1 concentrations of structurally related analogues. It is concluded that the apical membrane of gill cells has a very low passive permeability to amino acids, and that the overall permeability of the gill can be increased in a reversible fashion by exposure to reduced salinity or to high external concentrations of amino acid.
GIHS: A Generalized Color Model and Its Use for the Representation of Multiparameter Medical Images

It is often desirable to display medical images of different parameters in correlation to each other. Multiparameter color images can be used to represent such information. We discuss the most common color models in computer graphics, presented in a new unifying framework. A new generalized color model, GIHS, is presented of which the existing color models are special cases realized by particular choices of parameter values. The use of the GIHS model for the representation of multiparameter images in general and some medical applications are discussed.
275. Optimization of IL13Rα2-Specific CAR T Cells for Clinical Development Using Orthotopic Human Glioblastoma Models in NSG Mice

Standard-of-care therapies for glioblastoma (GBM), the most aggressive and common type of glioma, are inadequate, resulting in an unacceptably poor median overall survival of approximately 15 months following primary diagnosis. Immunotherapeutic targeting of brain tumors offers the opportunity to redirect the potency and specificity of the immune system to improve therapeutic outcomes. Our research program has developed a CAR T cell immunotherapy for GBM targeting IL-13 receptor α2 (IL13Rα2), a cell surface receptor over-expressed by the majority of high-grade gliomas. We have optimized second-generation IL13Rα2-specific CAR T cells, incorporating enhancements in CAR design and T cell engineering to improve T cell persistence and antitumor potency. These include a second-generation CAR containing the 41BB (CD137) costimulatory signaling domain (IL13BBζ-CAR), and a manufacturing strategy using an enriched central memory T cell (TCM) population for genetic engineering. In order to optimize clinical parameters for translating this therapy to patients, we have used orthotopic human GBM models in NSG mice. For these studies we have utilized the IL13Rα2-expressing primary low-passage GBM tumor sphere line PBT030-2, which has been engineered to express both EGFP and firefly luciferase (ffLuc) reporter genes (PBT030-2 EGFP:ffLuc). We first compared the route of delivery, intravenous (i.v.) or intracranial (i.c.), for mediating optimal antitumor activity against invasive TS-initiated PBT030-2. We found that i.c. delivery of the therapeutic CAR T cells elicited superior antitumor efficacy as compared to i.v. administration, which provided no therapeutic benefit. In a multifocal disease model, we also establish that CAR T cells that were injected i.c. at one tumor site were able to traffic to a second tumor site in the contralateral hemisphere. Performing CAR T cell titration studies, we estimate that approximately one CAR T cell is required for every two IL13Rα2 tumor cells based on volumetric analysis of day 8 PBT030-2 tumors. Further, we evaluated whether CAR positivity impacted therapeutic efficacy, as our product release criteria for the clinical trial requires the therapeutic product to be at least 10% CAR positive. Indeed, we found equivalent efficacy for i.c. delivered T cells of either 10% versus 100% CAR positivity when cell doses were standardized by CAR, suggesting that unengineered T cells do not negatively impact the therapeutic potency of the CAR T cells. Finally, we evaluated the impact of corticosteroid, given its frequent use in clinical management of GBM, and demonstrate that low dose dexamethasone does not diminish T cell antitumor activity in vivo. These findings provide the rational for initiating a first-in-human clinical trial with intracranial administration of IL13Rα2-specific CD4+ CD8+ IL13BBζ-CAR T cells for the treatment of GBM.
O'Brien, Gerald V. Framing the Moron: The Social Construction of Feeble-Mindedness in the American Eugenic Era Manchester: Manchester University Press 224 pp., $24.95, ISBN 9780719087097 Publication Date: April 2013

Gerald V. O'Brien is professor of social work at Southern Illinois University, Edwardsville. Framing the Moron: The Social Construction of Feeble-Mindedness in the American Eugenic Era, which is di...
La construcción contra el desarrollo: dos maneras distintas de entender la gestación humana (Construction versus Development: Two Distinct Ways to Understand Human Gestation)

Spanish Abstract: Mucho apoyo al aborto, sea para el aborto libre o sea para el aborto solo por ciertos causales, se debe no a una desvalorizacion de la vida humana, sino a una erronea concepcion acerca del proceso de gestacion. Esta falsa concepcion trata a la gestacion como un proceso de construccion o fabricacion dentro del vientre materno, y no como el proceso de desarrollo conocido por la ciencia moderna. Como veremos, un ente en construccion no esta presente hasta que su construccion haya sido esencialmente completada, mientras que un ente en desarrollo esta presente durante todo el proceso. Por ultimo, atenderemos a la falta de imaginacion que causa este error, y a las maneras de superarla. English Abstract: Much support for abortion is founded not on a devaluation of human life but rather on an erroneous conception of the process of gestation. This false conception treats gestation as a process of construction or making within the womb, and not as the process of development known to modern science. As we shall see, an entity under construction is not present before us until its construction is essentially complete, while a developing entity is present during the entire process of development. Finally, we shall examine the lack of imagination at the root of the erroneous construction model of gestation, and its remedies.
Physical Interaction via Dynamic Primitives

Humans out-perform contemporary robots despite vastly slower ‘wetware’ (e.g. neurons) and ‘hardware’ (e.g. muscles). The basis of human sensory-motor performance appears to be quite different from that of robots. Human haptic perception is not compatible with Riemannian geometry, the foundation of classical mechanics and robot control. Instead, evidence suggests that human control is based on dynamic primitives, which enable highly dynamic behavior with minimal high-level supervision and intervention. Motion primitives include submovements (discrete actions) and oscillations (rhythmic behavior). Adding mechanical impedance as a class of dynamic primitives facilitates controlling physical interaction. Both motion and interaction primitives may be combined by re-purposing the classical equivalent electric circuit and extending it to a nonlinear equivalent network. It highlights the contrast between the dynamics of physical systems and the dynamics of computation and information processing. Choosing appropriate task-specific impedance may be cast as a stochastic optimization problem, though its solution remains challenging. The composability of dynamic primitives, including mechanical impedances, enables complex tasks, including multi-limb coordination, to be treated as a composite of simpler tasks, each represented by an equivalent network. The most useful form of nonlinear equivalent network requires the interactive dynamics to respond to deviations from the motion that would occur without interaction. That suggests some form of underlying geometric structure but which geometry is induced by a composition of motion and interactive dynamic primitives? Answering that question might pave the way to achieve superior robot control and seamless human-robot collaboration.
miRNAs As Critical Epigenetic Players in Determining Neurobiological Correlates of Major Depressive Disorder

Failure in eliciting proper adaptive response toward chronic stress stimuli often results in developing serious mental disabilities like major depressive disorder (MDD). Risk factors associated with adverse environmental condition are mostly found to be influential in pattering the neuromolecular architecture and functional output of depressed brain. Improper functioning of plasticity-related genes and stress-associated factors are often considered the terminal effect of this environmental modulation, causing an overall dysfunction in neuronal information processing pathway. Emerging concept of epigenetic perturbation has successfully established the role of microRNA (miRNA) in shaping the genetic information processing in disrupted neuromolecular circuitry of depressed brain. This has found to be persuasive in creating a strong epigenetic interface between environmental stimuli and underlying reversible changes in gene expression. Hence, the current chapter is primarily oriented to enumerate those MDD-related miRNA changes accountable for causing dysregulated downstream gene expression with etiopathogenic effects and their possible amelioration.
Lactation Duration and Progression to Diabetes in Women Across the Childbearing Years: The 30-Year CARDIA Study

Importance Lactation duration has shown weak protective associations with incident diabetes (3%-15% lower incidence per year of lactation) in older women based solely on self-report of diabetes, studies initiated beyond the reproductive period are vulnerable to unmeasured confounding or reverse causation from antecedent biochemical risk status, perinatal outcomes, and behaviors across the childbearing years. Objective To evaluate the association between lactation and progression to diabetes using biochemical testing both before and after pregnancy and accounting for prepregnancy cardiometabolic measures, gestational diabetes (GD), and lifestyle behaviors. Design, Setting, and Participants For this US multicenter, community-based 30-year prospective cohort study, there were 1238 women from the Coronary Artery Risk Development in Young Adults (CARDIA) study of young black and white women ages 18 to 30 years without diabetes at baseline (1985-1986) who had 1 or more live births after baseline, reported lactation duration, and were screened for diabetes up to 7 times during 30 years after baseline (1986-2016). Exposures Time-dependent lactation duration categories (none, >0 to 6 months, >6 to Main Outcomes and Measures Diabetes incidence rates per 1000 person-years and adjusted relative hazards (RH) with corresponding 95% CIs, as well as proportional hazards regression models adjusted for biochemical, sociodemographic, and reproductive risk factors, as well as family history of diabetes, lifestyle, and weight change during follow-up. Results Overall 1238 women were included in this analysis (mean [SD] age, 24.2 [3.7] years; 615 black women). There were 182 incident diabetes cases during 27 598 person-years for an overall incidence rate of 6.6 cases per 1000 person-years (95% CI, 5.6-7.6); and rates for women with GD and without GD were 18.0 (95% CI, 13.3-22.8) and 5.1 (95% CI, 4.2-6.0), respectively (Pfor difference Conclusions and Relevance This study provides longitudinal biochemical evidence that lactation duration is independently associated with lower incidence of diabetes. Further investigation is required to elucidate mechanisms that may explain this relationship.
Interdivisional Healthcare Committee: Speaking with One Voice on Cross-Cutting Issues in Health Care Psychology

One of the greatest challenges facing psychology in health settings today is the need for unification on critical issues of client access, workforce oversupply, education and training, and outcomes evalutions. Health care psychology specialty areas can no longer afford to operate in parallel. A unified vision is needed to overcome threats to the viability of the profession and to maximize the potential for achieving common goals. The current paper describes the formation of the Interdivisional Healthcare Committee (IHC), whose purpose is to establish a common agenda for promoting the professional, educational, and scientific goals of health care psychology. The IHC's initiative to develop new CPT codes for increasing access to psychologists' services in health care settings is outlined.
Length of the second stage of labor and preterm delivery risk in the subsequent pregnancy.

Background Cervical injury is regarded as an important risk factor for preterm delivery. A prolonged second stage of labor may increase the risk of cervical injury that, in turn, may be associated with increased risk of spontaneous preterm delivery in the subsequent pregnancy. Objective We sought to evaluate whether the duration of the second stage of labor in a term primiparous singleton delivery is associated with an increased risk of singleton spontaneous preterm delivery ( Study Design We carried out a retrospective cohort analysis of women with 2 consecutive pregnancies: a first term (≥37 weeks) delivery and second birth. Data were derived from a single institution’s prospectively collected obstetrical database from January 2005 through January 2015. Duration of the second stage of labor was examined as a continuous variable, modeled based on nonparametric restricted cubic regression spline with 4 degrees of freedom. Second-stage duration was also examined as short ( Results In all, 6715 women met inclusion criteria. The hazard of spontaneous preterm delivery in the second pregnancy trended higher with both shorter and longer second-stage labors. The length of the second stage of labor in the first term delivery was categorized as short ( Conclusion The risk of spontaneous preterm delivery in the second pregnancy was increased in women with a prolonged (≥180 minutes) second stage in the first term pregnancy. This risk was even greater among women who were delivered by cesarean in the first pregnancy.
Alcohol Intake and Weight Loss During Intensive Lifestyle Intervention for Adults with Overweight or Obesity and Diabetes.

Objective This study aimed to assess whether alcohol consumption decreases during an intensive lifestyle intervention (ILI) and whether alcohol consumption is associated with weight loss among participants with overweight or obesity and type 2 diabetes. Methods Participants (n = 4,901) were from the Action for Health in Diabetes (Look AHEAD) study, a randomized controlled trial that compared an ILI with a diabetes support and education (DSE) control. Mixed-effects models were used to estimate the effect of the ILI on alcohol consumption and the influence of alcohol consumption on weight loss at year 4. Results ILI and DSE participants did not differ in changes in alcohol consumption. Alcohol intake was not associated with weight loss at year 1 of the ILI. ILI participants who abstained from alcohol lost 5.1% ± 0.3% of initial weight at year 4 compared with a significantly (P = 0.04) smaller 2.4% ± 1.3% for consistent heavy drinkers. ILI participants who abstained from alcohol consumption over the 4 years lost 1.6% ± 0.5% more weight relative to individuals who drank alcohol at any time during the intervention (P = 0.003). DSE participants did not differ in weight loss by alcohol consumption. Conclusions Heavy alcohol drinkers are at risk for suboptimal long-term weight loss. Decreasing alcohol consumption may improve weight management among individuals with diabetes.
Logic: A Very Short Introduction

The 2nd edition of Graham Priest’s Logic: A Very Short Introduction updates the original version of the book, which appeared in 2000. This new version consists of the original thirteen chapters, re...
Gas Bubbles in Electrochemical Gas Evolution Reactions

Electrochemical gas evolution reactions are of vital importance in numerous electrochemical processes including water splitting, chloralkaline process, and fuel cells. During gas evolution reactions, gas bubbles are vigorously and constantly forming and influencing these processes. In the past few decades, extensive studies have been performed to understand the evolution of gas bubbles, elucidate the mechanisms of how gas bubbles impact gas evolution reactions, and exploit new bubble-based strategies to improve the efficiency of gas evolution reactions. In this feature article, we summarize the classical theories as well as recent advancements in this field and provide an outlook on future research topics.
Lessons learned from a single‐surgeon series of paediatric robot‐assisted laparoscopic urological procedures: predictors of high‐grade postoperative complications

OBJECTIVES To describe postoperative complications after robot-assisted laparoscopic urological surgery in children, and identify potential predictors of these complications by analysing the outcomes of a large-volume single-surgeon experience. PATIENTS AND METHODS We reviewed our institutional database to identify all robot-assisted laparoscopy (RAL) cases performed between December 2007 and December 2017. Patients were grouped into three cohorts based on the anatomical location of the procedure: upper urinary tract (kidney and renal pelvis); lower urinary tract (ureter); and lower urinary tract reconstruction with bowel (bladder reconstruction). A descriptive analysis of baseline characteristics, intra-operative variables and postoperative outcomes was carried out. All complications were graded using the Clavien-Dindo scale, and grouped based on type and time of occurrence ( 90 days). Multivariable logistic regression analysis was performed to identify predictors of high-grade complications (Clavien-Dindo grade ≥ III). We also measured complication rates based on year of surgery and surgical caseload. RESULTS Our database included a total of 326 patients, of whom 57% (n = 186) underwent upper urinary tract procedures, 30% (n = 97) ureteric procedures, and 13% bladder reconstruction. The median follow-up for each procedure was 13, 11 and 57 months, respectively. Of the total, 10 cases were converted to an open approach and excluded from further analysis. The most common types of complication in all groups were infections (urinary tract infections) and urinary complications (urine leaks and urolithiasis). Bladder reconstructive procedures, which require the use of bowel, presented the highest rate of high-grade complications (32%). Length of hospital stay (LOS; odds ratio [OR] 1.33, confidence interval [CI] 1.16-1.53), estimated blood loss (EBL) in surgery (OR 1.01, CI 1.002-1.019) and operating time (OR 1.004, CI 1.002-1.006) were all associated with increased odds of high-grade complications on multivariate analysis (P < 0.05). CONCLUSIONS In this single-surgeon series, we have described the most commonly encountered complications after RAL in paediatric urology, finding rates similar to the complication rates reported in the current literature on other surgical approaches. In addition, LOS, operating time and EBL, which are probable surrogates of case complexity, were associated with increased odds of high-grade complications.
SparCE : Spar sity Aware General-Purpose C ore E xtensions to Accelerate Deep Neural Networks

Deep Neural Networks (DNNs) have emerged as the method of choice for solving a wide range of machine learning tasks. The enormous computational demand posed by DNNs is a key challenge for computing system designers and has most commonly been addressed through the design of DNN accelerators. However, these specialized accelerators utilize large quantities of multiply-accumulate units and on-chip memory and are prohibitive in area and cost constrained systems such as wearable devices and IoT sensors. In this work, we take a complementary approach and improve the performance of DNNs on general-purpose processor (GPP) cores. We do so by exploiting a key attribute of DNNs, viz. sparsity or the prevalence of zero values. We propose Sparsity-aware Core Extensions (SparCE) - a set of low-overhead micro-architectural and ISA extensions that dynamically detect whether an operand (e.g., the result of a load instruction) is zero and subsequently skip a set of future instructions that use it. To maximize performance benefits, SparCE ensures that the instructions to be skipped are prevented from even being fetched, as squashing instructions comes with a penalty (e.g., a pipeline stall). SparCE consists of 2 key micro-architectural enhancements. First, a Sparsity Register File (SpRF) is utilized to track registers that are zero. Next, a Sparsity-Aware Skip Address (SASA) Table is used to indicate instruction sequences that can be skipped, and to specify conditions on SpRF registers that trigger instruction skipping. When an instruction is fetched, SparCE dynamically pre-identifies whether the following instruction(s) can be skipped, and if so appropriately modifies the program counter, thereby skipping the redundant instructions and improving performance. We model SparCE using the gem5 architectural simulator, and evaluate our approach on 6 state-of-the-art image-recognition DNNs in the context of both training and inference using the Caffe deep learning framework. On a scalar microprocessor, SparCE achieves 1.11×-1.96× speedups across both convolution and fully-connected layers that exhibit 10-90 percent sparsity. These speedups translate to 19-31 percent reduction in execution time at the overall application-level. We also evaluate SparCE on a 4-way SIMD ARMv8 processor using the OpenBLAS library, and demonstrate that SparCE achieves 8-15 percent reduction in the application-level execution time.
Line mixing and broadening in the v(1→3) first overtone bandhead of carbon monoxide at high temperatures and high pressures

Abstract Temperature-dependent line mixing and line broadening parameters were empirically-determined for 17 rovibrational transitions in the v(1→3) bandhead of carbon monoxide near 2.3 µm. Collisional effects on the high rotational energy lines (E″ = 5500–8600 cm − 1 ) in the R-branch were studied over a range of temperatures from 1200–3750 K in a shock tube and heated gas cell. Measured spectra comprising the target lines in Ar and CO bath gases were fit with Voigt profiles at near-atmospheric pressures to determine line-broadening coefficients, with temperature dependence accounted by a power law. With line broadening established, line-mixing effects were examined at elevated pressures up to 60 atm at similar temperatures, reflecting conditions in high-pressure combustion environments. A modified exponential gap model for line mixing was developed to capture the pressure and temperature dependence of collisional transfer rates for the bandhead region using the relaxation matrix formalism.
Caesium thorium silicate, Cs2ThSi6O15

A caesium thorium(IV) silicate has been synthesized serendipitously under high-temperature solid-state conditions by the reaction of ThIV with a fused silica/alumina reaction crucible. The compound crystallizes in the orthorhombic space group Pca21. The crystal structure consists of ThO6 distorted octa­hedra corner-shared with SiO4 tetra­hedra to form an anionic three-dimensional framework possessing extended channels containing Cs+ cations. Cs2ThSi6O15 is a phyllosilicate with the same sheet structure as β-K3NdSi6O15.
A Successful CardioMEMS™ Implantation via Brachial Vein Access: A Case Report

Abstract The CardioMEMS™ HF system (Abbott, Chicago, IL), a wireless pulmonary artery (PA) pressure sensor, was approved by the FDA after demonstration of reduction of heart failure hospitalization in New York Heart Association class III patients. These devices are implanted into the desired PA branch via either common femoral or jugular vein access. However, in some patients who cannot undergo the procedure via these routine access sites for various reasons, alternative access is needed. We describe, to our knowledge, the first case of successful CardioMEMS™ implantation via brachial vein access.
The Interplay between Peripherin 2 Complex Formation and Degenerative Retinal Diseases

Peripherin 2 (Prph2) is a photoreceptor-specific tetraspanin protein present in the outer segment (OS) rims of rod and cone photoreceptors. It shares many common features with other tetraspanins, including a large intradiscal loop which contains several cysteines. This loop enables Prph2 to associate with itself to form homo-oligomers or with its homologue, rod outer segment membrane protein 1 (Rom1) to form hetero-tetramers and hetero-octamers. Mutations in PRPH2 cause a multitude of retinal diseases including autosomal dominant retinitis pigmentosa (RP) or cone dominant macular dystrophies. The importance of Prph2 for photoreceptor development, maintenance and function is underscored by the fact that its absence results in a failure to initialize OS formation in rods and formation of severely disorganized OS membranous structures in cones. Although the exact role of Rom1 has not been well studied, it has been concluded that it is not necessary for disc morphogenesis but is required for fine tuning OS disc size and structure. Pathogenic mutations in PRPH2 often result in complex and multifactorial phenotypes, involving not just photoreceptors, as has historically been reasoned, but also secondary effects on the retinal pigment epithelium (RPE) and retinal/choroidal vasculature. The ability of Prph2 to form complexes was identified as a key requirement for the development and maintenance of OS structure and function. Studies using mouse models of pathogenic Prph2 mutations established a connection between changes in complex formation and disease phenotypes. Although progress has been made in the development of therapeutic approaches for retinal diseases in general, the highly complex interplay of functions mediated by Prph2 and the precise regulation of these complexes made it difficult, thus far, to develop a suitable Prph2-specific therapy. Here we describe the latest results obtained in Prph2-associated research and how mouse models provided new insights into the pathogenesis of its related diseases. Furthermore, we give an overview on the current status of the development of therapeutic solutions.
Structure-based Design of Prefusion-stabilized SARS-CoV-2 Spikes

The COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2 has led to accelerated efforts to develop therapeutics, diagnostics, and vaccines to mitigate this public health emergency. A key target of these efforts is the spike (S) protein, a large trimeric class I fusion protein that is metastable and difficult to produce recombinantly in large quantities. Here, we designed and expressed over 100 structure-guided spike variants based upon a previously determined cryo-EM structure of the prefusion SARS-CoV-2 spike. Biochemical, biophysical and structural characterization of these variants identified numerous individual substitutions that increased protein yields and stability. The best variant, HexaPro, has six beneficial proline substitutions leading to ~10-fold higher expression than its parental construct and is able to withstand heat stress, storage at room temperature, and multiple freeze-thaws. A 3.2 A-resolution cryo-EM structure of HexaPro confirmed that it retains the prefusion spike conformation. High-yield production of a stabilized prefusion spike protein will accelerate the development of vaccines and serological diagnostics for SARS-CoV-2.
Semiotics and Sign-Types

LEARNING OBJECTIVES • After reading this chapter, you should be able to do the following: • Distinguish between icons, indexes, and symbols, and discuss examples of their co-occurrence. • Provide reasons to use the word “symbol” narrowly rather than as an umbrella term for all signs and sign-types. • Discuss the significance of context in relation to language and indexicality. • Discuss the relative frequency of icons and indexes among animals. • Understand why symbols might be evident only in the human world. • Describe the history of sign theories and their importance to cultures, particularly religious ideas and practices. • Discuss the intellectual traditions associated with Saussure, Jakobson, Peirce, and Bateson. Introduction We live in a world of signs. It is a world that can be explained in reference to the “semiotic” (now, more typically “semiotics”) of Charles Sanders Peirce (pronounced “purse”). Diverse phenomena – from the turning of sunflowers toward the sun to the process whereby DNA is transcribed as RNA (ribonucleic acid), which in turn is translated into proteins – can all be understood in terms of sign relations (Ji 2002). This chapter covers the following themes: signs, metasigns, and their dynamic relations one to another; semiotics or sign theories in history and culture; the sharply different sign theories of Ferdinand de Saussure and Charles Peirce; and Peirce's most famous triad (icons, indexes, and symbols), which he conceived of as three sign modalities. Signs Signs seem to breed and multiply in Peirce's theory. As we discussed in Chapter 2, signs include interpretants ; but they also produce interpretants, which are themselves new signs. Peirce distinguished several kinds of interpretants, including the “dynamical interpretants” (i.e., dynamic effects like that of the sun on the sunflower). Such is Peirce's vision of semiosis or sign production-reception-circulation – a “live-action” process-oriented model provided by the great philosopher himself. Keep in mind throughout this chapter, however, that although we talk about icons, indexes, and symbols as though they are things (sign-things), by the end of the book it should be clear that what is most interesting are the processes by which people produce (and use, circulate, and consume) signs, processes by which complex relationships are made to appear as icons.
A natural product biflavonoid scaffold with anti-tryptase activity

Tryptase is a serine protease that is released from mast cells during allergic responses. Tryptase inhibitors are being explored as treatments for allergic inflammation in the skin and respiratory system, most notably asthma. Here we report direct tryptase inhibition by natural product compounds. Candidate inhibitors were identified by computational screening of a large (98,000 compounds) virtual library of natural product compounds for tryptase enzymatic site binding. Biochemical assays were used to validate the predicted anti-tryptase activity in vitro, revealing a high (four out of six) success rate for predicting binding using the computational docking model. We further assess tryptase inhibition by a biflavonoid scaffold, whose structure-activity relationship is partially defined by assessing the potency of structurally similar analogs.
Control of Complex Objects: Challenges of Linear Internal Dynamics

Physical interaction with an object that has internal dynamics can be challenging, both for humans and robots. An example is carrying a cup of coffee, where the nonlinear dynamics between the cup and the liquid can be chaotic and unpredictable. This study examined how nonlinearity of an object’s dynamics contributed to the difficulty of a task and if linearization of the object dynamics facilitated performance. Human subjects did a task in a virtual set-up with a haptic interface using a robotic manipulandum. The task of transporting a cup of coffee was reduced to a 2D cart-and-pendulum model; subjects moved the cart and felt the dynamics of the pendulum representing sloshing coffee. Performance with the nonlinear system was compared to a linearized mass-spring version of the system. Subjects (n=16) executed continuous rhythmic, self-paced movements. In the linearized system subjects chose to move at frequencies close to the resonant frequencies and clearly avoided the anti-resonance frequency. In the nonlinear system subjects did not avoid the anti-resonance frequency. To evaluate performance, mutual information quantified predictability between the interaction force and the cup and object dynamics. Mutual information was lower in trials when the cup moved close to the anti-resonance frequency in both linear and nonlinear systems. The magnitudes of the interaction forces were higher in the linear system, especially at frequencies slightly below the anti-resonance. These results run counter to the expectation that linearization would simplify this task. These findings may be useful as design considerations for robot control and human-robot interaction: if humans interact with robots that exhibit complex dynamics in the frequency range of human actions, linearizing a nonlinear system may potentially disturb intuitive and low-effort cooperation.
Understanding how health systems facilitate primary care redesign

Objective To understand how health systems are facilitating primary care redesign (PCR), examine the PCR initiatives taking place within systems, and identify barriers to this work. Study setting A purposive sample of 24 health systems in 4 states. Study design Data were systematically reviewed to identify how system leaders define and implement initiatives to redesign primary care delivery and identify challenges. Researchers applied codes which were based on the theoretical PCR literature and created new codes to capture emerging themes. Investigators analyzed coded data then produced and applied a thematic analysis to examine how health systems facilitate PCR. Data collection Semi-structured telephone interviews with 162 system executives and physician organization leaders from 24 systems. Principal findings Leaders at all 24 health systems described initiatives to redesign the delivery of primary care, but many were in the early stages. Respondents described the use of centralized health system resources to facilitate PCR initiatives, such as regionalized care coordinators, and integrated electronic health records. Team-based care, population management, and care coordination were the most commonly described initiatives to transform primary care delivery. Respondents most often cited improving efficiency and enhancing clinician job satisfaction, as motivating factors for team-based care. Changes in payment and risk assumption as well as community needs were commonly cited motivators for population health management and care coordination. Return on investment and the slower than anticipated rate in moving from fee-for-service to value-based payment were noted by multiple respondents as challenges health systems face in redesigning primary care. Conclusions Given their expanding role in health care and the potential to leverage resources, health systems are promising entities to promote the advancement of PCR. Systems demonstrate interest and engagement in this work but face significant challenges in getting to scale until payment models are in alignment with these efforts.
A review of interstellar rocketry fundamentals.

To reach even the nearest stars in a human lifetime requires a ship speed that is a substantial fraction of the speed of light. This means an enormous kinetic energy investment in the ship and suggests that maximizing the efficiency may be more important than minimizing the mass ratio. This paper develops the pertinent relativistic rocket equations and finds the conditions for high kinematic efficiency. Using the limiting efficiency of percent, the minimum energy needed for one-way and for round trip voyages, and to explore all 'good' suns out to a given distance, using prefueled rockets, is determined. Savings due to refueling the rocket (and reloading propellant) at the destination and in flight are both somewhat greater than 2:1.
Multilingual Language Policies and the Continua of Biliteracy: An Ecological Approach

The one language—one nation ideology of language policy and national identity is no longer the only available one worldwide (if it ever was). Multilingual language policies,which recognize ethnic and linguistic pluralism as resources for nation-building, are increasingly in evidence. These policies, many of which envision implementation through bilingual intercultural education, open up new worlds of possibility for oppressed indigenous and immigrant languages and their speakers,transforming former homogenizing and assimilationist policy discourses into discourses about diversity and emancipation. This article uses the metaphor of ecology oflanguage to explore the ideologies underlying multilingual language policies, and the continua of biliteracy framework as ecological heuristic for situating the challenges faced in implementing them. Specifically, the paper considers community and classroom challenges inherent in implementing these new ideologies,as they are evident in two nations which introduced transformative policies in the early 1990s: post-apartheid South Africa's newConstitution of 1993 and Bolivia's National Education Reform of 1994. It concludes with implications for multilingual language policies in the United States and elsewhere.
Characterizing the nature of discourse in mathematics classrooms

A key idea in mathematics education reform today is the need to support discourse in classrooms. Despite the importance of this goal however, research has shown that realizing this vision of discourse can be hard to achieve. To address this issue, I introduce a framework that can be used to study and implement discourse in mathematics classrooms. Data come from two second-grade classrooms in which instruction was based on a reform-based curriculum. The study examines the character of the discourse that occurred in these two classrooms. I first identify six distinct discourse structures that were used as building blocks for talking about students' solutions to mathematical problems. I also identify three broad patterns in the ways these structures were used to define interactions in the classrooms. These patterns vary in the level of complexity from getting discourse started to increasingly complex patterns where students were engaging in mathematically complex discussions.
Psicoterapia e Medicina Geral e Familiar – o potencial da terapia cognitivo comportamental

The increasing prevalence of mental disorders, their costs, and the effects of the current economic crisis reinforce the need for psychological intervention in medical care. The World Health Organization (WHO) has stated that half of all the suffering associated with health and disease in Western countries is due to mental disorders, particularly depression and anxiety. Research has demonstrated the effectiveness of psychological interventions. The benefits of psychological intervention can occur in conditions not necessarily related to mental disorders such as cardiovascular diseases, cancer, rheumatoid arthritis, diabetes, chronic pain, and others. These benefits cause a reduction in the use of medical services and the use of medication, and promote greater adherence to therapy, as well as behavioral change. Cognitive therapy has low costs and a high success rate. Interest in mental health and the conditions caused by mental distress motivated the author to explore different types of psychotherapy that could be effective in primary care. The family physician can make use of some of the techniques of cognitive therapy. However time devoted to psychotherapy in parallel to the usual medical consultation may complement it. Application of CBT techniques in psychotherapy enhances medical practice and contributes to the whole-person approach.
Tb, Pr, and Ce dopants in YBa2Cu3O7−δ

Data for YBa 2 Cu 3 O 7 doped with Tb, Pr, and Ce are interpreted in terms of (i) superconductivity in the BaO planes (not in the CuO 2 planes), and (ii) the behaviors of YBa 2 Cu 3 O 7 when doped by Tb, Pr, or Ce.
Many-Electron wave function and momentum density

Summary for the review talk on recent progress in the theoretical studies of electron momentum density distribution at the Sagamore XIII conference (Stare Jablonki, Poland; September 3-9, 2000).
Coming Up Short: The United States' Second-Best Strategies for Corralling Purely Speculative Derivatives

Purely speculative derivatives (PSDs) are derivatives in which neither counterparty is engaged in hedging. Unless used for entertainment purposes, PSDs are irrational, less-than-zero-sum transactions. Entities that engage in PSDs jeopardize their stakeholders and increase systemic risk. PSDs can also increase moral hazard, be used for regulatory arbitrage, and redirect resources away from efficient allocation of market capital. PSDs should be unenforceable, void for public policy reasons, except where expressly permitted to provide gambling entertainment, enhance price discovery, or increase liquidity for hedgers. In the U.S., however, PSDs are often legal and enforceable, even after the financial crisis of 2008 that was exacerbated by PSDs. Several provisions of the Commodities Exchange Act (CEA) and the Dodd-Frank Act indirectly address some of the threats of PSDs. These strategies include increased clearing requirements, increased capital and margin requirements, required information reporting, elimination of previous regulatory exemptions, prohibition against proprietary trading for certain commercial banks, and a declaration that no bailout financing will be given to financial entities speculating in derivatives. These strategies, however, do not eliminate PSDs or their problems. At best, they discourage firms from entering into PSDs. The extent of discouragement, however, is unclear. At worst these second-best strategies do little to decrease PSD costs and risks. There is statutory space within the CEA, however, to allow courts and federal regulatory authorities to aggressively restrict PSDs while permitting them where socially beneficial. This space is a function of themes permeating the CEA — the disfavorable treatment of over-the-counter (OTC) derivatives, the concern for the public benefit, the favorable treatment of hedging transactions, the disfavorable treatment of speculating transactions, and the promotion of price discovery and hedger liquidity. Appropriate regulation of PSDs would help avert future financial disasters and foster the efficient allocation of capital.
Collective caching: application-aware client-side file caching

Parallel file subsystems in today's high-performance computers adopt many I/O optimization strategies that were designed for distributed systems. These strategies, for instance client-side file caching, treat each I/O request process independently, due to the consideration that clients are unlikely related with each other in a distributed environment. However, it is inadequate to apply such strategies directly in the high-performance computers where most of the I/O requests come from the processes that work on the same parallel applications. We believe that client-side caching could perform more effectively if the caching subsystem is aware of the process scope of an application and regards all the application processes as a single client. In this paper, we propose the idea of "collective caching" which coordinates the application processes to manage cache data and achieve cache coherence without involving the I/O servers. To demonstrate this idea, we implemented a collective caching subsystem at user space as a library, which can be incorporated into any message passing interface implementation to increase its portability. The performance evaluation is presented with three I/O benchmarks on an IBM SP using its native parallel file system, GPFS. Our results show significant performance enhancement obtained by collective caching over the traditional approaches.