cssi/SciSciGPT-SciSciNet huggingface dataset:
Viral delivery of shRNA to amygdala neurons leads to neurotoxicity and deficits in Pavlovian fear conditioning

Abstract The use of viral vector technology to deliver short hairpin RNAs (shRNAs) to cells of the nervous system of many model organisms has been widely utilized by neuroscientists to study the influence of genes on behavior. However, there have been numerous reports that delivering shRNAs to the nervous system can lead to neurotoxicity. Here we report the results of a series of experiments where adeno-associated viruses (AAV), that were engineered to express shRNAs designed to target known plasticity associated genes (i.e. Arc, Egr1 and GluN2A) or control shRNAs that were designed not to target any rat gene product for depletion, were delivered to the rat basal and lateral nuclei of the amygdala (BLA), and auditory Pavlovian fear conditioning was examined. In our first set of experiments we found that animals that received AAV (3.16E13–1E13 GC/mL; 1 μl/side), designed to knockdown Arc (shArc), or control shRNAs targeting either luciferase (shLuc), or nothing (shCntrl), exhibited impaired fear conditioning compared to animals that received viruses that did not express shRNAs. Notably, animals that received shArc did not exhibit differences in fear conditioning compared to animals that received control shRNAs despite gene knockdown of Arc. Viruses designed to harbor shRNAs did not induce obvious morphological changes to the cells/tissue of the BLA at any dose of virus tested, but at the highest dose of shRNA virus examined (3.16E13 GC/mL; 1 μl/side), a significant increase in microglia activation occurred as measured by an increase in IBA1 immunoreactivity. In our final set of experiments we infused viruses into the BLA at a titer of (1.60E+12 GC/mL; 1 μl/side), designed to express shArc, shLuc, shCntrl or shRNAs designed to target Egr1 (shEgr1), or GluN2A (shGluN2A), or no shRNA, and found that all groups exhibited impaired fear conditioning compared to the group which received a virus that did not express an shRNA. The shEgr1 and shGluN2A groups exhibited gene knockdown of Egr1 and GluN2A compared to the other groups examined respectively, but Arc was not knocked down in the shArc group under these conditions. Differences in fear conditioning among the shLuc, shCntrl, shArc and shEgr1 groups were not detected under these circumstances; however, the shGluN2A group exhibited significantly impaired fear conditioning compared to most of the groups, indicating that gene specific deficits in fear conditioning could be observed utilizing viral mediated delivery of shRNA. Collectively, these data indicate that viral mediated shRNA expression was toxic to neurons in vivo , under all viral titers examined and this toxicity in some cases may be masking gene specific changes in learning. Therefore, the use of this technology in behavioral neuroscience warrants a heightened level of careful consideration and potential methods to alleviate shRNA induced toxicity are discussed.
Photon assisted Levy flights of minority carriers in n-InP

Abstract We study the photoluminescence spectra of n-doped InP bulk wafers, both in the reflection and the transmission geometries relative to the excitation beam. From the observed spectra we estimate the spatial distribution of minority carriers allowing for the spectral filtering due to reabsorption of luminescence in the wafer. This distribution unambiguously demonstrates a non-exponential drop-off with distance from the excitation region. Such a behavior evidences an anomalous photon-assisted transport of minority carriers enhanced owing to the high quantum efficiency of emission. It is shown that the transport conforms very well to the so-called Levy-flights process corresponding to a peculiar random walk that does not reduce to diffusion. The index γ of the Levy flights distribution is found to be in the range γ = 0.64 –0.79, depending on the doping. Thus, we propose the high-efficiency direct-gap semiconductors as a remarkable laboratory system for studying the anomalous transport.
Embolic atrial myxoma causing aortic and carotid occlusion

Abstract Background Cardiac myxomas are a rare but well-described cause of stroke that usually occur in young people. Cardiac myxoma can embolize to multiple sites throughout the body. Case Description A 45-year-old woman presented acutely with altered mental status and signs of lower extremity vascular occlusion. Pathologic studies confirmed the diagnosis of cardiac myxoma. Conclusions This is the first case reported in the English literature of simultaneous aortic and internal carotid artery occlusion from embolism of an atrial myxoma without evidence of intracardiac tumor on transesophageal echocardiogram.
Mixing simulation of a viscous Newtonian liquid in a twin sigma blade mixer

The flow of a viscous Newtonian fluid in a twin sigma blade mixer over the course of a blade cycle is simulated using FEM with mesh superposition, and the resulting velocity profiles are used to calculate the paths of material points in order to do an analysis of the distributive mixing and overall efficiency of the mixer over time. Visual inspection of the material-point distribution, as well as mixing measures that include the cluster distribution index, scale of segregation and mean length of stretch showed the overall mixing effectiveness of this mixer, although there was some positions that had better distributive and stretch capability than others. The mean time-averaged efficiency was related to the specific blade positions and found to remain above zero, while its standard deviation was reducing over time, indicating that the majority of the material points were experiencing equivalent levels of stretching over time. © 2006 American Institute of Chemical Engineers AIChE J, 2006
Early identification of reading disabilities within an RTI framework

Early and accurate identification of children at risk for reading disabilities (RD) is critical for the prevention of RD within a response to intervention framework. In this study, we investigated the use of universal screening and progress monitoring for the early identification of RD in kindergarten children. A total of 366 children were administered a battery of screening measures at the beginning of kindergarten and progress-monitoring probes across the school year. A subset of children who showed initial risk for RD also received a 26-week Tier 2 intervention. Participants' achievement in word reading accuracy and/or fluency was assessed at the end of first grade. Results indicated that a screening battery containing measures of letter naming fluency, phonological awareness, rapid naming, or nonword repetition accurately identified good and poor readers at the end of first grade. Findings also showed that children's response to supplemental and/or classroom instruction measured in terms of growth in letter naming fluency added significantly to the prediction of reading outcomes.
Structure: Organizing Your Documents

When discussing the organization of documents, Aristotle said, “A whole is that which has a beginning, middle, and ending” This approach is a good way to examine the organization of general scientific documents, such as reports and articles.
Inferring the Causal Direction Privately

Causal inference deals with identifying which random variables "cause" or control other random variables. Recent advances on the topic of causal inference based on tools from statistical estimation and machine learning have resulted in practical algorithms for causal inference. Causal inference has the potential to have significant impact on medical research, prevention and control of diseases and identifying influential factors that impact society to name just a few. However, these promising applications for causal inference are often ones that involve sensitive or personal data of users that need to be kept private (e.g. medical records, personal finances). Therefore, there is a need for the development of causal inference methods that preserve data privacy. We study the problem of inferring causality using the current, popular causal inference framework, the additive noise model (ANM) while simultaneously ensuring privacy of the users. We derive a framework that provides differential privacy guarantees for a variety of ANM variants. We run extensive experiments, and demonstrate that our techniques are practical and easy to implement.
Characteristics of chronic megacolon among patients diagnosed with multiple endocrine neoplasia type 2B

BackgroundGastrointestinal symptoms are frequent in multiple endocrine neoplasia (MEN) 2B and may be related to megacolon.ObjectiveThe objective of this article is to review the clinical features o...
Recycling of Paper Products

Paper is recycled at a relatively high rate in the U.S. Rates are particularly high for corrugated boxes, which are predominantly recovered from businesses rather than from households. Packaging is a major source of recycled paper, as well as a major market for the recycled fiber. Paper coated with plastic or wax is difficult to recycle. The paper-recycling process involves re-suspending the fibers in the slurry, and separating contaminants. Recycled fibers tend to be shorter and weaker than virgin fibers. Contaminants in the recycled paper can cause problems with operation of the process as well as with paper performance. With proper design, recycled paper can perform very similarly to paper made from virgin fiber.
Pediatric Glioma: Role of Platelet-Derived Growth Factor Receptor

Abundant evidence exists, especially in adult patients, implicating a critical role for PDGFR in the pathogenesis of human gliomas, including induction of primary oncogenesis as well as the maintenance of established glioma survival, growth, invasive spread, angiogenesis, and progression from lower to higher grades. More recent evidence also points towards a central role for PDGFR in maintaining neural stem cells in adults and in the possible recruitment of cancer stem cells and other CNS progenitor and facilitating cells leading to the development and progression of gliomas. Although the data are more limited in comparison to that described in the adult literature, emerging evidence now indicates that PDGFR amplification is the single most common genetic alteration in pediatric high-grade gliomas, including diffuse intrinsic pontine gliomas. However, the expression patterns and potential functional roles of PDGFR in gliomas may be distinct between adults and children. Investigations to establish the functional role and clinical relevance of PDGFR expression and PDGFR activity in childhood glioma are ongoing. Despite the lack of success to date of targeted PDGFR inhibitors in clinical trials for the treatment of high-grade gliomas, PDGFR remains an attractive target for the development of novel therapeutic strategies for gliomas given the critical role that PDGFR signaling plays in oncogenic growth- and survival-promoting pathways.
Characteristics of the Swirling Flow in a Multipoint LDI Combustor

An experimental investigation was conducted to study the aerodynamic characteristics of the non-reacting, swirling flow field associated with a Multipoint Swirl-Venturi Lean Direct Injection (LDI) combustor. There are 9 fuel injectors designed to fit within a 76.2 mm square area, which is approximately the same area of a conventional fuel injector. Each individual fuel injector has a helical axial-vaned swirler with a short internal convergentdivergent venturi to provide rapid mixing of the fuel and air and to provide a small recirculation zone for burning. The fuel injector is inserted through the center of swirler and the fuel tip is at the throat of the venturi. All the swirlers have same tip vane angles of 60o with the calculated swirl number of 1.0. Two different swirler arrangements were investigated experimentally, which include a co-swirling array, where all swirlers acted in the same direction, and a counter-swirling array, where the swirl direction alternated for adjacent swirlers. A 3-D Particle Image Velocimetry (PIV) system was employed to investigate the instantaneous vortex structure of the swirling flow and to measure the mean velocity components and Reynolds stresses. A two-component Laser Doppler Velocimetry (LDV) system was employed to get the benchmark quality data which are planned for validating the state-of-the-art numerical models in addition more advanced LES approach. Detailed experimental data are provided to improve mechanistic understanding of the multipoint swirler generated flow field. The experimental results indicate that the flow structures change significantly as compared with the single swirler test. There are very strong interactions among the adjacent swirlers near the swirler exit.
Noise and Fluctuations in Multiphoton Processes

In multiphoton processes atoms respond in a nonlinear way to (laser) light and its fluctuations.1–14 An atom absorbing a number of photons is sensitive not only to the mean intensity and bandwidth of the light, but also to the kind and details of the fluctuations, i.e., to the higher-order statistics of the radiation field. During the past few years we have gained a considerable theoretical understanding of photon correlation effects in resonant multiphoton processes.
Leopoldstadt, Judenplatz, and Beyond

Discussions of Jews’ relationship to Vienna before 1938 tend to focus on their consumption of Viennese culture, including music, art, literature, and intellectual innovation. However, understanding place as a formative aspect of material culture can help us see another crucial aspect of how Jews—individually and collectively—came to terms with their place in the city. This essay examines the significance of place for Jews in Vienna through a variety of primary sources related to the Judenplatz, the square which is today the city’s premier site of Jewish memory, and Leopoldstadt, the district that encompasses Vienna’s most densely populated Jewish residential area. Memoirs, newspaper articles, caricatures, and maps written by both Jews and non-Jews reveal how the significance of these two areas changed over time, as they became deeply intertwined with the self-perceptions of both Jews and non-Jews. Analyzing how the Judenplatz and Leopoldstadt engaged Jewish difference over time helps us understand how the presence or absence of Jews remained a persistent dialectic in determining the meaning of place in Vienna.
On the Tone of English Advertisements

Advertisements,which have become inevitable in people's life,have uniqueness in vocabulary,syntax,and tone. This article attempts to analyze the tones in English and Chinese advertisements.Through diction,sentence pattern and punctuation,we can create different tones.As we know,some tones can help attract the readers and make them take purchasing actions.By knowing the chief tones in advertisements in English countries,we will find a better way to advertise the Chinese products,which is very important in international markets.
Chickenpox and pregnancy. What are the risks

PreviewChickenpox (ie, varicella) during pregnancy is usually benign, but there are a few significant exceptions. The possibility of complications, fetal or perinatal infection, and mortality varies with the onset and severity of the disease. Dr Rosenfeld reviews the clinical manifestations of varicella in the general population and discusses the specific risks for pregnant women and infants.
Application note: A hardware method for time-stamping asynchronous serial data streams relative to GNSS time

A method for precisely synchronizing an external serial data stream to the pulse-per-second (PPS) output signal from global navigation satellite-based systems (GNSS) receiver is described in this paper. A signal timing device was designed that used a digital signal processor (DSP) with serial inputs and input captures to generate time-stamps based on an internal timer. All temporal measurements were made directly in hardware, which eliminated any concerns of software latency. The resolution of the signal timing device was [email protected] Testing showed that time measurements made on the signal timing device were consistent with measurements made using a digital oscilloscope. The standard error between the signal timing device and digital oscilloscope was [email protected] which translated to less than a millimeter of horizontal position error for agricultural operations at speeds less than 10m/s. The signal timing device was shown to be useful for synchronizing GNSS receivers with ground based position measurement systems used to assess dynamic accuracy in agricultural applications by mitigating error due to latency.
Social Science Foundations of a Mestizo Theory of Personality and Psychiatry

The discovery of America meant not only the geographical exploration of new lands, but also the unveiling of a spiritual new world … the life cycle of Spanish America gravitates around behavioral patterns indelibly established in pre-Columbian times, some of which are still alien to traditional European standards.
Usage of Existing Meteorological Data Networks for Parameterized Road Ice Formation Modeling

AbstractA road ice prediction model was developed on the basis of existing data networks with an objective of providing a computationally efficient method of road ice forecasting. Icing risk was separated into three distinct road ice formation mechanisms: hoarfrost, freezing fog, and frozen precipitation. Hoarfrost parameterizations were mostly gathered as presented in previous literature, with modifications incorporated to account for diffusional ice crystal growth-rate complexity. Freezing-fog parameterizations were based on previous fog typological analyses under the assumption that fog formation mechanisms are similar in above- and subfreezing temperatures. Frozen-precipitation parameterizations were primarily unique to the developed model but were also partially based on previous research. Diagnostic analyses use a synthesis of Automated Surface Observing System (ASOS), Automated Weather Observing System (AWOS), and Oklahoma Mesonet data. Prognostic analyses utilize the National Digital Forecast Data...
Methods and novel technology for microRNA quantification in colorectal cancer screening

The screening and diagnosis of colorectal cancer (CRC) currently relies heavily on invasive endoscopic techniques as well as imaging and antigen detection tools. More accessible and reliable biomarkers are necessary for early detection in order to expedite treatment and improve patient outcomes. Recent studies have indicated that levels of specific microRNA (miRNA) are altered in CRC; however, measuring miRNA in biological samples has proven difficult, given the complicated and lengthy PCR-based procedures used by most laboratories. In this manuscript, we examine the potential of miRNA as CRC biomarkers, summarize the methods that have commonly been employed to quantify miRNA, and focus on novel strategies that can improve or replace existing technology for feasible implementation in a clinical setting. These include isothermal amplification techniques that can potentially eliminate the need for specialized thermocycling equipment. Additionally, we propose the use of near-infrared (NIR) probes which can minimize autofluorescence and photobleaching and streamline quantification without tedious sample processing. We suggest that novel miRNA quantification tools will be necessary to encourage new discoveries and facilitate their translation to clinical practice.
Muconic Acid Production via Alternative Pathways and a Synthetic “Metabolic Funnel”

Muconic acid is a promising platform biochemical and precursor to adipic acid, which can be used to synthesize various plastics and polymers. In this study, the systematic construction and comparative evaluation of a modular network of non-natural pathways for muconic acid biosynthesis was investigated in Escherichia coli, including via three distinct and novel pathways proceeding via phenol as a common intermediate. However, poor recombinant activity and high promiscuity of phenol hydroxylase ultimately limited “phenol-dependent” muconic acid production. A fourth pathway proceeding via p-hydroxybenzoate, protocatechuate, and catechol was accordingly developed, though with muconic acid titers by this route reaching just 819 mg/L, its performance lagged behind that of the established, “3-dehydroshikimiate-derived” route. Finally, these two most promising pathways were coexpressed in parallel to create a synthetic “metabolic funnel” that, by enabling maximal net precursor assimilation and flux while preserv...
Transforming Training in Orientation and Mobility: Examining the Effect Using an Audio-Link on the Distance Between Trainer and Trainee

Increased distances between instructor and trainee during orientation and mobility (O&M) training is purported to be associated with improved outcomes...
Husserl and Geiger on Feelings and Intentionality

How are we conscious of our feelings? The question was a controversial topic among German psychologists between the end of the nineteenth century and the beginning of the twentieth century. In 1911 Moritz Geiger made his contribution to the debate with a paper titled “Das Bewusstsein von Gefuhle”. Husserl read Geiger’s text and sketched an alternative answer to the question about the manifestation of feelings. Geiger’s and Husserl’s texts dealt with the problem of intentionality and object orientation of feelings: are feeling object oriented? Geiger’s answered that, in feelings, consciousness is sometimes not oriented to representations (and, therefore, that object-intentionality is not an essential property of the mind), while Husserl incorporated object-intentionality in the broader structure of time-consciousness.
Long-Crack Fatigue Thresholds and Short Crack Simulation at Liquid Helium Temperature

A short crack simulation (SCS) test is used to characterize the near—threshold fatigue crack growth behavior of stainless steels at 4 K. The test methodology holds the maximum stress intensity factor constant while increasing the minimum stress intensity factor, thus raising the stress ratio from 0.1 at the start to about 0.8 at the end of the test. The resulting fatigue crack growth rate measurements are unaffected by crack closure, and the intrinsic threshold is directly obtained without a correction factor. Merits of the test procedure are described.
Abstract 3790: The TIA Admission Score - A Tool to Determine Observation Versus Inpatient Admission Status for TIA

BACKGROUND: Centers for Medicare and Medicaid Services has criteria for admission to observation vs. inpatient status, one of which is expected discharge within 24 hours. Validated scores predictin...
Comparing structures of stiffness matrices using invariants

The stiffness of a compliant coupling that connects two rigid bodies together is a geometric mapping, and in the plane, it transforms an axis of rotation into a line of force. For this mapping, there are important invariants, most evident of which is the signature of the stiffness matrix, which is shown to dictate the possibilities for the second derivative of potential energy, that is, whether potential energy is concave-up, concave-down, or passing through an inflection point or through a saddle point.
Diagnosis of Dysplasia in Ulcerative Colitis by Combined Light Microscopy and Scanning Electron Microscopy

Patients with longstanding and extensive ulcerative colitis (UC) are at increased risk for the development of colonic carcinoma (1–3). The tumors tend to afflict younger patients and to present at an advanced stage of growth (4–7). To prevent this complication or to detect early lesions, it has been recommended that high risk patients have periodic surveillance by endoscopy and mucosal biopsy to identify epithelial dysplasia (8–12). Alternative terms for dysplasia have included precancer, adenomatous epithelium and precarcinoma (13–15). Dysplasia is defined as a neoplastic transformation and serves as a marker that the patient has or is exceptionally prone to develop a carcinoma (16). The finding of dysplasia, especially when it is associated with a mass lesion or when it persists in repeat biopsies, justifies serious consideration of a total colectomy even when there is no overt carcinoma evident (9,17). Dysplasia is currently identified by the light microscopic (LM) analysis of mucosal biopsies, but difficulties are often encountered in distinguishing dysplasia from the effects of active inflammation on the colonic epithelium (16). To assist in this distinction, we have employed scanning electron microscopy (SEM) with quantitative analyses which can be done in conjunction with standard light microscopy (18,19). This review will provide details of the LM and SEM studies and other techniques used in the diagnosis of epithelial dysplasia.
Autoimmune Endocrine Disorders

Autoimmune endocrine disorders are common conditions evaluated for and treated by pediatric endocrinologists. Recognition of the underlying autoimmunity associated with the disorders and disease associations is critical to providing appropriate care for these patients. Autoimmune endocrine disorders coexist in recognized syndromes known as the autoimmune polyendocrine syndromes (APS): APS-1 or autoimmune polyendocrinopathy candidiasis and ectodermal dystrophy (APECED) and APS-2. More rare autoimmune endocrine disorders include the immunodysregulation polyendocrinopathy enteropathy X-linked (IPEX) syndrome. This rare disorder presents in infancy with type 1 diabetes and enteropathy. In this chapter, we will discuss the pathophysiology of the autoimmune process, the underlying genetics and disease associations of the autoimmune polyendocrine syndromes, and treatment and screening protocols and briefly touch on rare autoimmune endocrine disorders.
Experiments and Modeling in Plasticity of Fibrous Composites

This paper describes a part of a continuing program in experimental verification of model predictions of the overall inelastic behavior of fibrous metal matrix composites. Measurements of initial and subsequent yield surfaces, and of plastic strains were performed on thin—walled B/Al tubes with unidirectional axial reinforcement, under torsion and internal pressure that was applied along a complex incremental path. The results were interpreted with three different models, the periodic hexagonal array (PHA) model, the bimodal plasticity theory, and a modified Mori—Tanaka scheme. The reliability of the predictions varies significantly, particularly where plastic strains are concerned. Only the PHA model appears to be of value in this regard, but the shape and position of overall yield surfaces was well predicted even by the matrix-dominated mode of the bimodal theory.
The Limits of Presidential Power: A Citizen's Guide to the Law — Table of Contents and Introduction

Written for a general audience, this guide provides an overview of the laws governing presidential power in the United States. It begins with an overview of the federal government. It then discusses the powers that the law provides a president, as well as the tools a president might use to exercise those powers. These include executive orders, involvement in agency rulemaking, and the exercise of enforcement-related discretion. The guide then identifies and explores legally supported checks on presidential power (emanating from Congress, the Executive Branch, the federal courts, state governments, and non-governmental actors) before turning to a case study: the evolution of climate change policy in the United States. The guide concludes with suggestions for how individuals can use their knowledge of the laws of presidential power to more effectively participate in politics. The accompanying download provides the book’s table of contents and its introduction only.
Plasma Ameliorates Endothelial Dysfunction in Burn Injury.

Abstract Background A complex inflammatory response mediates the systemic effects of burn shock. Disruption of the endothelial glycocalyx causes shedding of structural glycoproteins, primarily syndecan-1 (SDC-1), leading to endothelial dysfunction. These effects may be mitigated by resuscitative interventions. Materials and methods Sprague–Dawley rats were used to create small, medium, and large burns and uninjured controls. Three different intravenous resuscitation protocols were applied within each group: Lactated Ringer's (LR) alone, LR plus fresh frozen plasma (FFP), or LR plus albumin. Blood was serially collected, and plasma SDC-1 was quantified with enzyme-linked immunosorbent assay. In one cohort, Evan's Blue Dye (EBD) was administered and quantified in lung by spectrophotometry as a functional assay of vascular permeability. In a second cohort, intact SCD-1 was quantified by immunohistochemistry in lung tissue. Statistical analysis employed two-way analysis of variance with multiple comparisons and Student's t-test. Results EBD extraction from lung was significantly greater with higher injury severity versus controls. Extraction decreased significantly in large-burn animals with addition of FFP to LR versus LR-only; addition of albumin to LR did not decrease EBD extraction. Plasma SCD-1 increased in injured animals compared with controls, and changes correlated with injury severity in all resuscitation groups (significance, P Conclusions Addition of FFP, not of albumin, to post-burn resuscitation diminishes vascular leakage associated with large burns. Addition of colloid does not affect SDC-1 shedding as measured in plasma. Ongoing work will further define pathophysiologic mechanisms and potential therapeutic interventions to mitigate injury and promote repair of the endothelial glycocalyx.
What Should the Next President Do? A Search for a Path for All

The purpose of the chapter is to identify what policy initiatives need to take place in the USA to achieve equity for African-Americans. The research of Murphy and Cunningham (Organizing for Community Controlled Development: Renewing Civil Society. SAGE Publications, Thousand Oaks, CA, 2003), Dennis and Lourie (Everything is Normal until Proven Otherwise: A Book about Wraparound Services. CWLA Press, Washington, DC, 2006), Iverson and Armstrong (Jobs Aren’t Enough: Toward a New Economic Mobility for Low-Income Families. Temple University Press, Philadelphia, 2006), Miller and Hess (Community Policing: Partnerships for Problem Solving. Wadsworth Publishing, Boston, 2013), Tighe and Mueller (The Affordable Housing Reader. Routledge, New York, 2013), Goldsmith (2016) and Miller (Economic Development for Everyone: Creating Jobs, Growing Businesses, and Building Resilience in Low Income Communities. Routledge, New York, 2017) informed this focus group agenda. In addition, the topic was shaped by reports from the W. K. Kellogg Foundation (TRHT Implementation Handbook, 2016) and The Ferguson Commission (Forward through Ferguson: A Path Toward Racial Equity, 2015). Five central points emerged from the conversation. One, most of the discussants did not think that meaningful action would come from the federal government. Two, efforts at restorative justice could not just rely on political or legislative initiatives. A re-ordering of America’s socio-political structure was necessary. Three, mitigation of segregation could not be limited to housing. Mitigation of segregation in employment and education was also crucial. Four, lasting racial change in America depended upon a fundamental transformation of the mindset of both African Americans and whites toward one another. Five, true equity for African Americans was the only meaningful long-term goal for race relations in America. In the accompanying essay, “The Day After Segregation: Thinking Through the Unimaginable,” Jonathan Smith makes a distinction between what race is and what race does. For him, the main purpose of race is to spatially separate people. Smith points out that the use of race to segregate African Americans has resulted in their exploitation. Yet, that same segregation has been used by African Americans to define their “blackness” and the boundaries of what they call home. For Smith, Americans—both white and black—will not be able to imagine a world without segregation until they recognize this paradox.
Fast Triangle Counting Using Cilk

Triangle counting is a representative graph analysis algorithm with several applications. It is also one of the three benchmarks used in the IEEE HPEC Graph Challenge. Triangle counting can be expressed as a graph algorithm and in a linear algebra formulation using sparse matrix-matrix multiplication (SpGEMM). The linear algebra formulation using the SpGEMM algorithm in the Kokkoskernels library was one of the fastest implementations for the triangle counting problem in last year's Graph Challenge. This paper improves upon that work by developing an SpGEMM implementation that relies on a highly efficient, work-stealing, multithreaded runtime. We demonstrate that this new implementation results in improving the triangle counting runtime up to 5× to 12× on different architectures. This new implementation also breaks the 109 barrier for the rate measure on a single node for the triangle counting problem. We also compare the linear algebra formulation with a traditional graph based formulation. The linear algebra implementation is up to 2.96× to 7× faster on different architectures compared to the graph based implementation. Furthermore, we present analysis of the scaling of the triangle counting implementation as the graph sizes increase using both synthetic and real graphs from the graph challenge data set.
Andradite skarn garnet records of exceptionally low δ 18 O values within an Early Cretaceous hydrothermal system, Sierra Nevada, CA

Skarn garnets in the Mineral King roof pendant of the south–central Sierra Nevada within Sequoia National Park, California, USA reveal variable fluid chemistry with a significant component of meteoric water during metasomatism in the Early Cretaceous Sierra Nevada Batholith. We focus on andradite garnet associated with Pb–Zn mineralization in the White Chief Mine. Laser fluorination oxygen isotope analyses of δ18O of garnet (δ18O(Grt)) from sites along the skarn show a large range of values (− 8.8 to + 4.6‰ VSMOW). Ion microprobe (SIMS) analyses elucidate that individual andradite crystals are strongly zoned in δ18O(Grt) (up to 7‰ of variation). Total rare-earth element concentrations (∑REE) across individual garnets show progressive depletion of skarn-forming fluids in these elements during garnet growth. These findings support a skarn model of earliest red high-δ18O grandite garnet consistent with a magmatic-dominated equilibrium fluid (δ18O(H2O) as high as ≈ + 8‰). Later, green andradite crystallized in equilibrium with a low-δ18O fluid indicating a significant influx of meteoric fluid (δ18O(H2O) ≈ − 6 to − 5‰), following a hiatus in garnet growth, associated with late-stage Pb–Zn mineralization. Latest orange overprint rims have higher δ18O values (δ18O(H2O) ≈ 0–2‰), and depleted total REEs, suggesting influx of high-δ18O, trace-element depleted fluid derived from regional metamorphism of the carbonate host. Remarkably, low δ18O(Grt) values in the White Chief canyon skarn require a significant proportion of meteoric fluid available during > 400 °C andradite-forming metasomatism. Fluid flow was channelized at the pluton–wallrock contact, evidenced by the narrow extent of skarn.
The 'Fixation Thesis' and Other Falsehoods

This Article challenges the so-called “fixation thesis” of public-meaning originalism. This thesis holds that the meaning of the Constitution was fixed when adopted and exists in the past as a fact, unaffected by what anyone thinks about it in the present. For public-meaning originalists, constitutional meaning is always ontologically “there” in the past to be found, even if their epistemological method sometimes fails to find it. The fixation thesis underwrites the powerful rhetoric of fidelity that public-meaning originalists deploy against nonoriginalists, whom they deride for “making up” constitutional meaning without any interpretive theory: “it takes a theory to beat a theory.” But there is a theory that contests public-meaning originalism, though most public-meaning originalists ignore it. Philosophical hermeneutics maintains that the meaning of any text is constituted by the present as well as the past. If this claim is true, then the fixation thesis must be false because the original public meaning of the Constitution could not exist in the past as a fact unaffected by the present. And if original public meaning is not “there” in the past to be found, public-meaning originalists are “making it up,” too, for no theory can discover meaning that does not exist. The few public-meaning originalists who address hermeneutics mistake it for a criticism of public-meaning methodology. But hermeneutics claims that the original public meaning does not exist, not that public-meaning methods do not work: original public meaning is simply not “there” in the past to be found. It doesn’t take an interpretive theory to beat public-meaning originalism—an ontology will do.
Evolving Concepts in the Evaluation and Management of Bladder Cancer in Elderly Men

In this article, the contemporary knowledge regarding specific issues related to the care of older bladder cancer patients is reviewed. The status of radical cystectomy, bladder-sparing strategies, checkpoint inhibition, prostate-sparing surgery, and BCG distribution pertaining to older adults are discussed. The use of minimally invasive approaches for radical cystectomy in patients with invasive bladder cancer is on the rise, including those patients with advanced age. Enhanced recovery pathways are improving time-to-recovery for patients undergoing radical cystectomy which may be especially important in the elderly and frail. Trimodal bladder-sparing strategies are emerging options for patients who are unfit for radical cystectomy. Immunotherapies offer promising options for patients with advanced or treatment-refractory disease. Prostate-sparing surgery does not currently hold a place in the contemporary management of bladder cancer for those patients who are surgical candidates. Older adults may be at risk of disparity in the distribution of scarce BCG resources during times of manufacturing shortage. Older adults, as compared with those younger, face special challenges in their bladder cancer care. There is a clinical imperative that practitioners involved in the evaluation and management of older bladder cancer patients be knowledgeable of the unique issues that stand between them and cancer-free survival.
Stimulus-choice (mis)alignment in primate MT cortex

Abstract For stimuli near perceptual threshold, the trial-by-trial activity of single neurons in many sensory areas is correlated with the animal’s perceptual report. This phenomenon has often been attributed to feedforward readout of the neural activity by the downstream decision-making circuits. The interpretation of choice-correlated activity is quite ambiguous, but its meaning can be better understood in the light of population-wide correlations among sensory neurons. Using a statistical nonlinear dimensionality reduction technique on single-trial ensemble recordings from the middle temporal area during perceptual-decision-making, we extracted low-dimensional neural tra jectories that captured the population-wide fluctuations. We dissected the particular contributions of sensory-driven versus choice-correlated activity in the low-dimensional population code. We found that the neural trajectories strongly encoded the direction of the stimulus in single dimension with a temporal signature similar to that of single MT neurons. If the downstream circuit were optimally utilizing this information, choice-correlated signals should be aligned with this stimulus encoding dimension. Surprisingly, we found that a large component of the choice information resides in the subspace orthogonal to the stimulus representation inconsistent with the optimal readout view. This misaligned choice information allows the feedforward sensory information to coexist with the decision-making process. The time course of these signals suggest that this misaligned contribution likely is feedback from the downstream areas. We hypothesize that this non-corrupting choice-correlated feedback might be related to learning or reinforcing sensory-motor relations in the sensory population. Author summary In sensorimotor decision-making, internal representation of sensory stimuli is utilized for the generation of appropriate behavior for the context. Therefore, the correlation between variability in sensory neurons and perceptual decisions is sometimes explained by a causal, feedforward role of sensory noise in behavior. However, this correlation could also originate via feedback from decision-making mechanisms downstream of the sensory representation. This cannot be resolved by analyzing single unit responses, but requires a population level analysis. Area MT contains both sensory and choice information and is known to be the key sensory area for visual motion perception. Thus the decision-making process may be corrupting the sensory representation. However, we find that the sensory stimuli and choice variables are separate at the population level,contradicting the previous interpretations based on single unit recordings. This new insight postulates how neural systems can maintain a mixed representation while allows learning and adaptation.
Active Voltage Balancing Methodology for Series connection of 1700V SiC MOSFETs

Series connection of 1.7kV Silicon Carbide (SiC) MOSFETs have potential to become a building block of compact and lightweight Megawatt power converters. These devices with high current carrying capability (56.5A/die) can be connected in series to develop high voltage and current rating power converters. Series connection of power devices generally involves passive voltage balancing methods, such as R-C snubbers, which increases the switching loss in power converters. Therefore, this paper describes the series connection of 1.7kV SiC MOSFETs using Active Voltage Balancing method. Active Voltage Balancing avoids R-C snubbers for minimizing voltage mismatch, thus reducing the switching loss in power converters. An alternative method of Active Voltage Balancing has been discussed in the paper for series connection of two 1.7kV SiC MOSFETs. The proposed method has been verified by simulation and experimental results.
Beyond the Brain: The Systemic Pathophysiological Response to Acute Ischemic Stroke

Stroke research has traditionally focused on the cerebral processes following ischemic brain injury, where oxygen and glucose deprivation incite prolonged activation of excitatory neurotransmitter receptors, intracellular calcium accumulation, inflammation, reactive oxygen species proliferation, and ultimately neuronal death. A recent growing body of evidence, however, points to far-reaching pathophysiological consequences of acute ischemic stroke. Shortly after stroke onset, peripheral immunodepression in conjunction with hyperstimulation of autonomic and neuroendocrine pathways and motor pathway impairment result in dysfunction of the respiratory, urinary, cardiovascular, gastrointestinal, musculoskeletal, and endocrine systems. These end organ abnormalities play a major role in the morbidity and mortality of acute ischemic stroke. Using a pathophysiology-based approach, this current review discusses the pathophysiological mechanisms following ischemic brain insult that result in end organ dysfunction. By characterizing stroke as a systemic disease, future research must consider bidirectional interactions between the brain and peripheral organs to inform treatment paradigms and develop effective, comprehensive therapeutics for acute ischemic stroke.
Cycles in Causal Learning.

In the causal learning setting, we wish to learn cause-and-effect relationships between variables such that we can correctly infer the effect of an intervention. While the difference between a cyclic structure and an acyclic structure may be just a single edge, cyclic causal structures have qualitatively different behavior under intervention: cycles cause feedback loops when the downstream effect of an intervention propagates back to the source variable. We present three theoretical observations about probability distributions with self-referential factorizations, i.e. distributions that could be graphically represented with a cycle. First, we prove that self-referential distributions in two variables are, in fact, independent. Second, we prove that self-referential distributions in N variables have zero mutual information. Lastly, we prove that self-referential distributions that factorize in a cycle, also factorize as though the cycle were reversed. These results suggest that cyclic causal dependence may exist even where observational data suggest independence among variables. Methods based on estimating mutual information, or heuristics based on independent causal mechanisms, are likely to fail to learn cyclic casual structures. We encourage future work in causal learning that carefully considers cycles.
Hematopoietic Stem Cell Stress and Regeneration

Hematopoietic stem cells (HSCs) propagate the hematopoietic system throughout the lifetime of an individual. Beyond homeostatic regulation, HSCs respond to many stressors, including infection, aging, irradiation, and chemotherapy, through distinct cellular and molecular pathways to restore homeostasis. Here, we review how HSCs and bone marrow niche cells respond to various stressors and their role in HSC regeneration. In this review, we summarize the manner in which HSCs respond to different stressors via intrinsic and extrinsic, and niche-driven mechanisms to support hematopoietic regeneration. We discuss recent work defining the cellular and molecular mechanisms by which HSCs respond to various forms of stress through specific alterations in cell cycling, DNA damage repair, and cell death. We also summarize the roles of recently defined bone marrow niche cell subtypes and niche-derived factors in mediating HSC regeneration. Stress through aging, inflammation, and myelosuppressive treatments significantly alters hematopoietic homeostasis, requiring HSCs to quickly respond to restore order. In the event that an inadequate HSC response occurs, patients are at risk for life-threatening complications such as hemorrhage, infection and bone marrow failure. In this review, we summarize recent work defining how HSCs respond to stress and the role of the bone marrow niche in HSC regeneration.
Novel Application of Photogrammetry to Quantify Fascicle Orientations of Female Cadaveric Pelvic Floor Muscles

Although critical for understanding and simulating pelvic floor muscle function and pathophysiology, the fascicle arrangements of the coccygeus and levator ani remain mostly undetermined. We performed close-range photogrammetry on cadaveric pelvic floor muscles to robustly quantify surface fascicle orientations. The pelvic floor muscles of 5 female cadavers were exposed through anatomic dissections, removed en bloc, and photographed from every required angle. Overlapping images were mapped onto in silico geometries and muscle fascicles were traced manually. Tangent vectors were calculated along each trace; interpolated to define continuous, 3D vector fields; and projected onto axial and sagittal planes to calculate angles with respect to the pubococcygeal line. Contralateral and ipsilateral pelvic floor muscles were compared within each donor (Kuiper’s tests) and using mean values from all donors (William-Watsons tests). Contralateral muscles and all but one ipsilateral muscle pair differed significantly within each donor (p < 0.001). When mean values were considered collectively, no contralateral or ipsilateral statistical differences were found but all muscles compared differed by more than 10° on average. Close-range photogrammetry and subsequent analyses robustly quantified surface fascicle orientations of the pelvic floor muscles. The continuous, 3D vector fields provide data necessary for improving simulations of the female pelvic floor muscles.