cssi/SciSciGPT-SciSciNet huggingface dataset:
Distinct Patterns of Tryptophan Maintenance in Tissues during Kynurenine Pathway Activation in Simian Immunodeficiency Virus-Infected Macaques

Induction of the kynurenine pathway (KP) of tryptophan catabolism has been proposed to contribute to T cell dysfunction during human/simian immunodeficiency virus (HIV/SIV) infection via depletion of local tryptophan levels and production of immunomodulatory KP metabolites. However, while changes in tryptophan and KP metabolites have been observed in plasma, their levels in lymphoid tissues and levels of enzymes downstream of indoleamine 2,3-dioxygenase (IDO1) have been relatively unexplored. We used our SIV-infected pigtailed macaque model to analyze longitudinal changes in KP metabolites and enzymes by gas chromatography/mass spectrometry and NanoString nCounter gene expression analysis, respectively, in spleen and blood compared to changes previously established in brain and CSF. We found that tryptophan levels were remarkably stable in tissue sites despite robust depletion in the circulating plasma and CSF. We also demonstrated that intracellular tryptophan reserves were maintained in cultured cells even in the presence of depleted extracellular tryptophan levels. Kynurenine, 3-hydroxykynurenine, quinolinic acid, and the KP enzymes all displayed highly divergent patterns in the sites examined, though IDO1 expression always correlated with local kynurenine/tryptophan ratios. Finally, we demonstrated by FACS that myeloid dendritic cells (mDCs) and cells of monocytic lineage were the highest producers of IDO1 in chronically infected spleens. Overall our study reveals insights into the tissue-specific regulation of KP enzymes and metabolites and, in particular, highlights the multiple mechanisms by which cells and tissues seek to prevent TRP starvation during inflammation.
On the Pathogenesis of Alzheimer's Disease: The MAM Hypothesis

The pathogenesis of Alzheimer's disease (AD) is currently unclear and is the subject of much debate. The most widely accepted hypothesis designed to explain AD pathogenesis is the amyloid cascade, which invokes the accumulation of extracellular plaques and intracellular tangles as playing a fundamental role in the course and progression of the disease. However, besides plaques and tangles, other biochemical and morphological features are also present in AD, often manifesting early in the course of the disease before the accumulation of plaques and tangles. These include altered calcium, cholesterol, and phospholipid metabolism; altered mitochondrial dynamics; and reduced bioenergetic function. Notably, these other features of AD are associated with functions localized to a subdomain of the endoplasmic reticulum (ER), known as mitochondria-associated ER membranes (MAMs). The MAM region of the ER is a lipid raft-like domain closely apposed to mitochondria in such a way that the 2 organelles are able to communicate with each other, both physically and biochemically, thereby facilitating the functions of this region. We have found that MAM-localized functions are increased significantly in cellular and animal models of AD and in cells from patients with AD in a manner consistent with the biochemical findings noted above. Based on these and other observations, we propose that increased ER-mitochondrial apposition and perturbed MAM function lie at the heart of AD pathogenesis.-Area-Gomez, E., Schon, E. A. On the pathogenesis of Alzheimer's disease: the MAM hypothesis.
Dietary Sphingomyelin Attenuates Inflammation and Metabolic Dysfunction in Diet- Induced Obese Mice

Current evidence indicates that dietary sphingomyelin (SM) is lipid-lowering and anti-inflammatory, although its potential to prevent chronic disease as part of the diet has not been fully explored...
Usefulness of the ElliPro Epitope Predictor Program in Defining the Repertoire of HLA-ABC Eplets

HLA matching at the epitope level offers new opportunities to identify suitable donors for transplant patients. The International HLA Epitope Registry (www.Epregistry.com.br) describes for the various HLA loci, repertoires of eplets including those that correspond to epitopes experimentally verified with specific antibodies. There are also many eplets which have remained as theoretical entities because no informative antibodies have been found. Which of them have immunogenic potential or conversely, might be considered as non-epitopes that cannot elicit specific antibody responses? This question is important for the application of epitope-based HLA matching in clinical transplantation. Correct predictions of B-cell epitopes on antigenic proteins are essential to the effective design of microbial vaccines and the development of specific antibodies used in immunotherapy and immunodiagnostics but prediction programs based on structural and physiochemical properties of amino acid residues are generally ineffective. Recent prediction programs based on three-dimensional structures of antigen-antibody complexes are more promising. One such program is called ElliPro developed by Ponomarenko. This report describes studies demonstrating that ElliPro can predict alloantibody responses to HLA-ABC eplets. Antibody-verified eplets have amino acid residues with much higher ElliPro scores than eplets for which no specific antibodies have been found. The latter group includes residues with very low ElliPro scores; they appear to represent eplets that might be classified as non-epitopes. In conclusion, ElliPro offers a new approach to characterize epitope repertoires that are clinically relevant in HLA matching.
Transporter engineering for cellobiose fermentation under lower pH conditions by engineered Saccharomyces cerevisiae

The aim of this study was to engineer cellodextrin transporter 2 (CDT-2) from Neurospora crassa for improved cellobiose fermentation under lower pH conditions by Saccharomyces cerevisiae. Through directed evolution, a mutant CDT-2 capable of facilitating cellobiose fermentation under lower pH conditions was obtained. Specifically, a library of CDT-2 mutants with GFP fusion was screened by flow cytometry and then serial subcultured to isolate a CDT-2 mutant capable of transporting cellobiose under acidic conditions. The engineered S. cerevisiae expressing the isolated mutant CDT-2 (I96N/T487A) produced ethanol with a specific cellobiose consumption rate of 0.069g/gcell/h, which was 51% and 55% higher than those of the strains harboring wild-type CDT-1 and CDT-2 in a minimal medium with 2g/L of acetic acid.
The Productive Efficiency Assessment of Wind Power Generation in the United States

Wind power is the largest renewable energy source which produces a negligible amount of GHG emissions, have gained enormous attention, especially in the electricity generation sector over the past decade in the United States. In this study, a Data Envelopment Analysis (DEA) is developed to quantitatively evaluate the relative efficiencies of the 34 state’s wind power productivity for the electricity generation. An output-oriented CCR (Charnes, Cooper, and Rhodes (1978)) and BCC (Banker, Charnes, and Cooper (1984)) models are applied to pre-determined two input and three output variables. The sensitivity analysis is conducted to test the robustness of the DEA models. The DEA results indicate that more than two-thirds of the states operate wind power efficiently even though there are only five states that reach the maximum efficiency score. Findings of this study shed some light on the current efficiency assessments of the states and the future of wind energy for both energy practitioners and policy makers.
Validity of cardiovascular data from electronic sources: The multi-ethnic study of atherosclerosis and HealthLNK

Background:Understanding the validity of data from electronic data research networks is critical to national research initiatives and learning healthcare systems for cardiovascular care. Our goal w...
A Splice Variant of Centrosomin Converts Mitochondria to Microtubule-Organizing Centers

Summary Non-centrosomal microtubule organizing centers (MTOCs) direct microtubule (MT) organization to exert diverse cell-type-specific functions. In Drosophila spermatids, the giant mitochondria provide structural platforms for MT reorganization to support elongation of the extremely long sperm. However, the molecular basis for this mitochondrial MTOC and other non-centrosomal MTOCs has not been discerned. Here we report that Drosophila centrosomin ( cnn ) expresses two major protein variants: the centrosomal form (CnnC) and a non-centrosomal form in testes (CnnT). CnnC is established as essential for functional centrosomes, the major MTOCs in animal cells. We show that CnnT is expressed exclusively in testes by alternative splicing and localizes to giant mitochondria in spermatids. In cell culture, CnnT targets to the mitochondrial surface, recruits the MT nucleator γ-tubulin ring complex (γ-TuRC), and is sufficient to convert mitochondria to MTOCs independent of core pericentriolar proteins that regulate MT assembly at centrosomes. We mapped two separate domains in CnnT: one that is necessary and sufficient to target it to mitochondria and another that is necessary and sufficient to recruit γ-TuRCs and nucleate MTs. In elongating spermatids, CnnT forms speckles on the giant mitochondria that are required to recruit γ-TuRCs to organize MTs and support spermiogenesis. This molecular characterization of the mitochondrial MTOC defines a minimal molecular requirement for MTOC generation and implicates the potent role of Cnn (or its related) proteins in the direct regulation of MT assembly and organization of non-centrosomal MTOCs.
N-series modules based on SST for mobile power substation

Mobile power substations (MPSs) are optimally designed to be installed on a truck bed for ease of transportation in order to provide an interface between two medium-voltage distribution systems under emergency or maintenance conditions. Based on the solid-state transformer (SST), a topology of N-series modules concept is proposed for MPS. The average control methods are used to balance the voltage and power for each SST module. The device losses are analyzed to estimate an upper limit to the theoretical system efficiency for a 5 MW–100 kHz MPS with 1.7-kV SiC MOSFET. Simulation results of three series-connected modules demonstrate the proposed MPS. A scale down prototype with three-series modules SST is build and parts of the system is tested.
Response by Madder et al to Letter Regarding Article, "Multimodality Intracoronary Imaging With Near-Infrared Spectroscopy and Intravascular Ultrasound in Asymptomatic Individuals With High Calcium Scores".

We agree with Drs Shaikh and Budoff on the necessity of additional studies to investigate whether detection of lipid-rich plaque (LRP) by near-infrared spectroscopy (NIRS) can add incremental value to the coronary artery calcium score (CACS) in the prediction of future cardiovascular events. In our recent study, we demonstrated that NIRS adds information on the presence or absence of LRP among individuals with a high CACS.1 A logical next step is to determine if …
HIV Prevention Drug’s Slow Uptake Undercuts Its Early Promise

Initially billed as a game changer, Truvada has faced multiple obstacles to widespread adoption.
Resolving National Forest Management Disputes

The process outlined in Chapter 9 is an experimental one. If pursued, it would provide the U.S. Forest Service and its constituent groups with the opportunity to try reaching agreement on selected issues that currently divide them and, in so doing, to determine the potential for resolving a wider spectrum of disputes in the agency. The procedural steps comprising this experimental process are designed to supplement existing Forest Service decision-making processes. They have been developed recognizing and reinforcing the statutory authority and responsibilities of the Forest Service in national forest management.
Spaces of Continuous Functions, Distributions, and Weak Derivatives

Let \(C_o(\mathbb {R}^N)\) denote the space of continuous functions of compact support in \(\mathbb {R}^N\), equipped with the sup-norm.
Underlying mechanisms and ecological consequences of variation in exploratory behavior of the Argentine ant, Linepithema humile

Uncovering how and why animals explore their environment is fundamental for understanding population dynamics, the spread of invasive species, species interactions etc. In social animals, individuals within a group can vary in their exploratory behavior and the behavioral composition of the group can determine its collective success. Workers of the invasive Argentine ant - Linepithema humile - exhibit individual variation in exploratory behavior, which affects the colony's collective nest selection behavior. Here we examine the mechanisms underlying this behavioral variation in exploratory behavior and determine its implications for the ecology of this species. We first establish that individual variation in exploratory behavior is repeatable and consistent across situations. We then show a relationship between exploratory behavior and the expression of genes that have been previously linked with other behaviors in social insects. Specifically, we find a negative relationship between exploratory behavior and the expression of the FOR gene. Finally, we determine how colonies allocate exploratory individuals in natural conditions. We find that ants from inside the nest are the least exploratory individuals, while workers on newly formed foraging trails are the most exploratory individuals. Furthermore, workers in the spring, when new resources emerge, are more exploratory than workers in the winter, potentially allowing the colony to find and exploit new resources. These findings reveal the importance of individual variation in behavior for the ecology of social animals and provide mechanistic and functional explanations for how such behavioral variation can emerge.
Identifying the regional extent and geochemical evolution of interbasin groundwater flow using geochemical inverse modeling and 87Sr/86Sr ratios in a complex conglomeratic aquifer

Abstract Interbasin groundwater flow (IGF) occurs when water that is recharged in one watershed or basin discharges into an adjacent watershed or basin. IGF can directly impact the water and solute mass discharged from a watershed and consequently, skew estimates of watershed-scale weathering rates. It is extremely difficult to determine the impact of IGF on weathering processes in adjacent watersheds because it is difficult to differentiate between solute mass originating within the watershed from solute mass transported into the watershed from sources outside the watershed. We quantify the regional extent of IGF in three watersheds (Canjilon, El Rito, and Vallecitos) draining the Tusas Mountains of northern New Mexico, USA (sites where IGF has been shown to occur) using spatial trends in 87Sr/86Sr in springs and streams and geochemical modeling using PHREEQC. 87Sr/86Sr ratios show a strong connection from the Canjilon watershed to the El Rito watershed and suggest that the IGF connection may extend to the Vallecitos watershed. Geochemical modeling constrained by XRD analysis of aquifer mineralogy indicates that IGF from the Canjilon watershed is the dominant control on perennial flow in springs and streams in the adjacent El Rito watershed. However, the geochemical signature of an IGF connection from El Rito to the Vallecitos watershed is weak to non-existent. The maximum possible IGF contribution from El Rito to Vallecitos is during snowmelt, contributing as much as 20% of the water and solute mass to Vallecitos. However, the maximum IGF contribution is
P088 Effect of leukoreduction of transfused blood products on deceased donor hla typing

Aim Deceased donor HLA typing is predicated on the assumption that the blood sample contains only DNA from the organ donor. Prior to procurement, most organ donors receive at least one unit of red blood cells (RBC), with some receiving >20, as part of life support or in order to maintain organ viability. Non-organ donor DNA acquired from transfusion may result in incorrect and/or ambiguous HLA typing, which could have dire consequences for the organ recipient. We investigated the impact of RBC transfusion on HLA typing with leukoreduced (LR) and non-LR RBCs. Methods To replicate the average total blood volume (TBV) of 5L, an in vitro model of 5 mL was used. Varying volumes of LR and non-LR donor RBCs (e.g. 0.25 mL in vitro = 1 RBC unit in vivo) were mixed to simulate different transfusion scenarios (Table). Typing was performed by real time PCR using Linkage Biosciences HLA typing kit (11 loci+: HLA - ABCDRDQDP SABR™ 384 Kits) and software (SureTyper™). Results For non-LR scenarios of 10 and 2 RBC units, PCR was unable to assign a definitive HLA type (i.e.“no call”) for multiple loci as >2 antigens per locus were detected. In the 1 non-LR RBC scenario, some loci had donor-specific positive wells that if ignored resulted in recipient typing. In contrast, both the 16 and 19 LR-RBC transfusion scenarios, which approach replacement of TBV, resulted in non-ambiguous recipient typing. Even when DNA concentration was low (3 ng/μl), recipient typing was assigned despite well drop-outs. Conclusions Our results show that HLA typing for deceased donors is differentially impacted by RBC LR status. Whereas non-LR RBCs can result in ambiguous or incorrect recipient typing, LR RBCs do not appear to preclude definitive typing results. Given that approximately half of the U.S. blood supply is non-LR, determining LR status has testing and clinical implications. If LR RBCs are given, regardless the volume, HLA typing should not be affected and there is no reason to delay typing for additional DNA material (e.g. lymph node, pre-transfusion sample). Download : Download high-res image (262KB) Download : Download full-size image
Schwann Cell Responses and Plasticity in Different Dental Pulp Scenarios.

Mammalian teeth have evolved as dentin units that enclose a complex system of sensory innervation to protect and preserve their structure and function. In human dental pulp (DP), mechanosensory and nociceptive fibers form a dense meshwork of nerve endings at the coronal dentin-pulp interface, which arise from myelinated and non-myelinated axons of the Raschkow plexus (RP). Schwann cells (SCs) play a crucial role in the support, maintenance and regeneration after injury of these fibers. We have recently characterized two SC phenotypes hierarchically organized within the coronal and radicular DP in human teeth. Myelinating and non-myelinating SCs (nmSCs) display a high degree of plasticity associated with nociceptive C-fiber sprouting and axonal degeneration in response to DP injuries from dentin caries or physiological root resorption (PRR). By comparative immunolabeling, confocal and electron microscopy, we have characterized short-term adaptive responses of SC phenotypes to nerve injuries, and long-term changes related to aging. An increase of SCs characterizes the early responses to caries progression in association with axonal sprouting in affected DP domains. Moreover, during PRR, the formation of bands of Bungner is observed as part of SC repair tracks functions. On the other hand, myelinated axon density is significantly reduced with tooth age, as part of a gradual decrease in DP defense and repair capacities. The remarkable plasticity and capacity of SCs to preserve DP innervation in different dental scenarios constitutes a fundamental aspect to improve clinical treatments. This review article discusses the central role of myelinating and non-mSCs in long-term tooth preservation and homeostasis.
Co-delivery of doxorubicin and erlotinib through liposomal nanoparticles for glioblastoma tumor regression using an in vitro brain tumor model.

Glioma is a highly malignant tumor that starts in the glial cells of brain. Tumor cells reproduce quickly and infiltrate rapidly in high grade glioma. Permeability of chemotherapeutic agents into brain is restricted owing to the presence of blood brain barrier (BBB). In this study, we developed a dual functionalized liposomal delivery system for efficient transport of chemotherapeutics across BBB for the treatment of glioma. Liposomes were surface modified with transferrin (Tf) for receptor targeting, and cell penetrating peptide PFVYLI (PFV) to increase translocation of doxorubicin (Dox) and Erlotinib (Erlo) across the BBB into glioblastoma (U87) tumor cells. In vitro cytotoxicity and hemolysis studies were performed to assess biocompatibility of liposomal nanoparticles. Cellular uptake studies demonstrated efficient internalization of Dox and Erlo in U87, brain endothelial (bEnd.3), and glial cells. In addition, dual functionalized liposomes showed significantly (p < 0.05) higher apoptosis in U87 cells. Significantly (p < 0.05) higher translocation of dual functionalized liposomes across the BBB and delivering chemotherapeutic drugs to the glioblastoma tumor cells inside PLGA-Chitosan scaffold resulted in approximately 52% tumor cell death, using in vitro brain tumor model.
CNValidator: validating somatic copy-number inference

Motivation CNValidator assesses the quality of somatic copy-number calls based on coherency of haplotypes across multiple samples from the same individual. It is applicable to any copy-number calling algorithm, which makes calls independently for each sample. This test is useful in assessing the accuracy of copy-number calls, as well as choosing among alternative copy-number algorithms or tuning parameter values. Results On a dataset of somatic samples from individuals with Barrett's Esophagus, CNValidator provided feedback on the correctness of sample ploidy calls and also detected data quality issues. Availability and implementation CNValidator is available on GitHub at https://github.com/kuhnerlab/CNValidator. Supplementary information Supplementary data are available at Bioinformatics online.
348 COST ANALYSIS OF SELF-INFLICTED FACIAL GUNSHOT WOUNDS: A CASE SERIES.

Purpose There are numerous studies on the topic of maxillofacial trauma, with focuses spanning from demographics to associated findings and related injuries; however, no study has yet specifically tackled the cost of maxillofacial trauma resulting from facial gunshot wounds. Recent technological advances have led to more aggressive and costly management of these injuries, but treatment protocols based on suitable outcomes have yet to be established. We aim to elucidate the significant expense of these injuries, paying particular attention to those requiring follow-up care and reconstructive surgery. Methods A total of 55 patients were identified at UNM Hospital (UNMH) from January 1995 to May 2004 by first searching for diagnostic codes related to facial trauma and then reviewing those charts individually. Each patient was cross-referenced in the UNMH billing database and the University Physician Associates (UPA) billing database. Forty-three patients had at least one entry in each database. Only billing entries related to the facial gunshot wound were included for final cost analysis. Demographic data included mean age 34 years, 95% male, and 33% privately insured. Results Total cost refers to UNMH plus UPA billing. The mean total cost was $76,640.67 per patient (n = 43). The highest total cost for any one patient was $352,158.52, and the lowest cost for an individual was $38,610.54. The mean total cost for patients who had at least one entry in either database at least 1 month from the time of injury was $119,832.57 (n= 22). The highest mean total cost for any patient in this population was $352,158.52. The lowest was $5,885.08. Conclusions Total cost of self-inflicted facial gunshot wounds is significant, with a mean per patient cost of over $75,000. Patients who remained at UNMH for follow-up care-determined as those with at least one billing entry 30 days from the incident-had a total mean per patient cost of nearly $120,000-a 56% increase. This figure is more impressive considering that some of these patients are still being treated. When the results of this study are weighed with patient insurance demographics of only one-third having private insurance, it becomes apparent that state and federal entities shoulder a significant portion of the cost of managing self-inflicted facial gunshot wounds. Based on the numbers revealed in this paper, open discussion and further research-including outcome studies comparing more expensive and often cosmetic procedures to functionally based interventions-are warranted.
Estimates of donated sperm use in the United States: National Survey of Family Growth 1995-2017

Objective To provide national estimates of donor insemination (DI) use in the United States and a description of the population of users. Design Population estimates were generated from nationally representative data through weighted proportions and count estimates. Setting Not applicable. Patient(s) Participants were U.S. women of childbearing age (15–44 years) sampled for interview in the National Survey of Family Growth. Intervention(s) None. Main Outcome Measure(s) Respondents who reported having received artificial insemination were asked the origin of the sperm. Responses could include husband/partner, donor only, or mixed donor and husband/partner. Result(s) In 1995, an estimated 170,701 (95% confidence interval 106,577–234,825) women had undergone DI using donor or mixed sperm. In 2015-2017, 440,986 (95% confidence interval 108,458–773,513) women were estimated to have used it. The DI users were mostly white, urban, older, college-educated, and had high family incomes. Conclusion(s) The DI use changed over time, from a decrease between 1995 and 2013 to a precipitous growth in 2015 to 2017. In recent years, nearly half a million women may be dealing with personal, relationship, and familial issues born of DI use. The United States does not maintain records on the usage of donor sperm, but better tracking of the use and outcomes of treatment would provide better estimates of the size of the affected population.
Applying Mathematical Set Theory to Statutory Construction of Municipal Sign Laws

The author discusses how an ambiguity in the town code of Southampton, New York, recently created a controversy over whether thin strips of plain plastic affixed to utility poles to demarcate a religious boundary would fall under the town’s definition of “signs.” The author explains how this case illustrates why municipal lawyers might want to review their high school mathematics lessons about set theory before drafting statutes. The application of set theory — particularly in the form of Venn diagrams — can help to prevent ambiguity of language in statutory construction. It is this ambiguity that gives rise to differences in interpretation, and these differences frequently lead to litigation over the meaning of a statute.
Cytokine tear film profile determination in eyes of healthy dogs and those with inflammatory periocular and skin disorders.

Abstract Alterations in serum cytokine levels and profiles have been reported in association with a variety of disease conditions (e.g., allergic, immune-mediated, etc.) in both humans and animals. In comparison to serum cytokine measurements, tear cytokine measurements might be expected to more accurately reflect the inflammatory milieu associated with periocular disease. The purpose of this study was to use a multiplexed assay to compare the cytokine profile of tears in healthy dogs to those with inflammatory skin and periocular disease. We were able to detect IL-2, IL-6, IL-8, and TNF-α in > 47 % of tear samples from both healthy canine patients and those with inflammatory dermatologic disease (with or without concurrent periocular involvement). In contrast, IL-7, IL-10 and IFN-γ were rarely detected. Dogs with both dermatologic and periocular disease (but not dermatologic disease alone) had higher levels of IL-8 (P 0.05, respectively) relative to healthy dogs. Patients with concurrent dermatologic and periocular disease also demonstrated significantly greater variability in IL-8 concentrations between eyes than did healthy dogs (P
Survival model methods for analyses of cancer incidence trends in young adults

Recent studies have reported increases in cancer incidence in adults under 50 years. However, there remains uncertainty about whether these are true increases or a result of incidental findings from increased medical imaging. To evaluate these trends, we propose an alternative method to age-period-cohort analyses based on survival modeling. Simulations show that our method is capable of quantifying cohort effects within various backgrounds including increasing medical imaging. We applied the method to analyze the changes in cancer incidence rates for 44 anatomic sites, stratified by sex, by birth cohort for individuals born from 1945 to 1969 in the US based on incidence data from the Surveillance, Epidemiology, and End Results (SEER) program, and tested the validity of our models using later birth cohorts (1970-1974 and 1975-1979). We found that cancer risks have increased significantly in 15 sites (9 in men and 11 in women) for 25-49 year-olds. These results were consistent with previous findings from age-period-cohort analyses. Furthermore, based on our simulations, these increases were independent of increased medical imaging and support substantial, increased extrinsic risks in the identified cancers. Although our approach has several limitations including the restriction to the younger age range and requirement of complete data for all ages of interest, we demonstrate many advantages of our approach including the ease in implementation and interpretation of cohort effects, robustness to various period backgrounds, and ability to make predictions. Our approach should help epidemiologists evaluate cohort effects using incidence data for cancer or other diseases.
Spinocerebellar ataxia type 6 family with phenotypic overlap with Multiple System Atrophy

Aim of the study. Multiple system atrophy (MSA) and spinocerebellar ataxia (SCA) share similar symptomatology. We describe a rare occurrence of familial MSA that proved to be SCA6 upon genetic analysis. Materials and methods. Eighty MSA patients were enrolled in our study; blood samples were collected and genetic screening of the familial case for known SCA loci was performed. Results. A 68-year-old woman presented with recurrent and severe episodes of light-headedness, imbalance, frequent falls, neck and lower back stiffness, subjective arm and leg weakness, and numbness and tingling in both feet. One year later, her condition had declined; she experienced more falls, worsening instability, again more generalised but still subjective weakness, impaired fine motor movements, slurred speech, difficulty swallowing, episodes of choking, bladder incontinence, and constipation. Clinical suspicion included parkinsonism, MSA, and SCA. The patient was enrolled in our MSA study and was found to have 22 and 12 CAG repeats in CACNA1A. The other 79 clinical MSA patients were negative for SCA6 screening. Conclusions and clinical implications. While MSA and SCA may have similar presentations during early disease stages, the presence of both conditions on the list of differential diagnoses can be a diagnostic dilemma. Further analysis will aid in developing a biomarker to distinguish between the two conditions and guide proper management.
Abstract IA03: Medulloblastoma predisposition according to molecular subgroup: The usual suspects and beyond

Cancer genomics has illuminated a wide spectrum of genes and core molecular processes contributing to human malignancy. Still, the genetic and molecular basis of many cancers remains only partially explained. Genetic predisposition accounts for 5-10% of cancer diagnoses, and genetic events cooperating with known somatic driver events are poorly understood. Analyzing established cancer predisposition genes in medulloblastoma (MB), a malignant childhood brain tumor, we recently identified pathogenic germline variants that account for 5-6% of all MB patients. The incidence of genetic predisposition to MB varied according to patient age and molecular subgroup status, with up to 25% of childhood SHH-MB patients predicted to harbor pathogenic germline variation. These estimates only account for known cancer predisposition genes, and ongoing studies designed to investigate unknown pathogenic events in the germline of MB patients have implicated novel MB predisposition genes. This presentation aims to summarize these recent insights into genetic predisposition to MB and contextualize these findings with their associated clinical implications. Citation Format: Paul A. Northcott. Medulloblastoma predisposition according to molecular subgroup: The usual suspects and beyond [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr IA03.
Managerial social capital and dividend smoothing

Abstract We investigate the influence of a previously unexamined managerial personal attribute, social capital, on a firm's propensity to smooth dividends. We document that greater managerial social capital is associated with a statistically and economically significant increase in dividend smoothing. The effect of social capital on dividend smoothing is stronger for financially constrained firms. We also find that social connections are positively associated with passive institutional ownership. Our results are robust to alternative model specifications, different variable measurement, and endogeneity tests. Overall, the findings are consistent with agency-based explanations for corporate dividend smoothing.
Serum Endothelin-1 Levels in Pediatric Patients after Cardiac Transplantation

Background and Hypothesis: Worldwide, approximately 650 pediatric heart transplants occur annually. Coronary artery vasculopathy (CAV) is the foremost cause of allograft failure following heart transplantation, accounting for more than 25% of deaths within one-year post transplant. Within 10 years, 30-45% of children will be diagnosed with CAV, yet the mechanism of disease is still misunderstood. Endothelin-1 (ET-1) has been shown to play an important role in development and promotion of CAV, however no studies have evaluated ET-1 levels in the pediatric population following heart transplant. Methods: All patients enrolled in the study have underwent cardiac transplant and present for annual cardiac catheterization and blood draw, with data being stored in a REDCAP database. Centrifuged plasma will be analyzed for ET-1 levels and compared to accepted standard pediatric values. Relationships between ET-1 levels and other lab values will be evaluated for correlation. Results: Currently awaiting plasma results. Conclusion and Potential Impact: This study will establish ET-1 levels in pediatric patients post cardiac transplantation. If ET-1 levels are correlated with CAV severity and are increased, ET-1 levels have the potential to be an inexpensive and easily available biomarker for continuing to monitor CAV progression. Using currently available ET-1 therapies such as ERAs has the potential to lower morbidity and mortality rates by delaying or reducing re-transplantation in patients with CAV.
Comparison of pediatric brain-dead donors to donation after circulatory death donors in the United States.

In pediatrics, an increasing need for transplantable organs exists. This study aimed to describe the epidemiology of pediatric deceased donors in the United States. This retrospective observational study utilized data from the Organ Procurement and Transplantation Network (OPTN) from 2000 to 2015. Patients were stratified based on method of organ donation. Demographic variables and mechanism of death were then compared. A total of 14,481 deceased pediatric organ donors, donation after brain death (DBD) and donation after circulatory death (DCD), were included in the study, of which 8% were DCD donors. A significant difference (p<0.001) existed between the two donor groups with respect to ethnicity and mechanism of death. The annual trend of DCD and DBD donors showed an inverse relationship. During the 15-year study period the number of DBD donors decreased from 985 to 785 per year while DCD donors increased from 15 to 146 per year. As well, overall organs transplanted per year decreased from 3,475 to 3,117 over the 15-year study period. Significant differences exist between pediatric DBD donors and DCD donors, specifically with respect to ethnicity and mechanism of death. The number of pediatric DBD donors is decreasing while the number of pediatric DCD is slowly rising, making it increasingly important to be able to characterize these donors to better identify eligible DCD donors to optimize organ utilization.
A new combination in Penstemon (Plantaginaceae)

The following new combination in Penstemon is made: Penstemon crandallii A. Nelson var. glabrescens (Pennell) C.C. Freeman.
Unified Position and Attitude Control of A Fully Nonlinear Quadrotor

This paper presents a departure from hierarchical cascade methods to control the position and attitude of a fully nonlinear quadrotor. The paper presents a nonlinear feedback control scheme that simultaneously controls position and attitude. The proposed method is based on a generalization of the Gauss's Principle of Least Constraint (GPLC) for higherorder constrained dynamical systems. By double differentiating the rigid-body position dynamics of a fully nonlinear quadrotor with respect to time, the translational and rotational dynamics become fully coupled at the levels of snap and angular acceleration, and the quadrotor is turned into a fully actuated system in a reduced configuration space. A generalized Baumgarte's error stabilization (BES) is developed to asymptotically drive constraint errors to zero. The nonlinear control law is due purely to the natural evolution of constrained system dynamics. To the best of our knowledge, this is the first instance that GPLC and BES are both extended to higher-order systems and that the control scheme for the position and attitude of a quadrotor is unified into one step by making use of its fully nonlinear constrained dynamics. The efficiency and efficacy of the proposed method is demonstrated by numerical experiments on a quadrotor tracking a prescribed conical spiral.
Lectures on Invariant Theory

The primary goal of this 2003 book is to give a brief introduction to the main ideas of algebraic and geometric invariant theory. It assumes only a minimal background in algebraic geometry, algebra and representation theory. Topics covered include the symbolic method for computation of invariants on the space of homogeneous forms, the problem of finite-generatedness of the algebra of invariants, the theory of covariants and constructions of categorical and geometric quotients. Throughout, the emphasis is on concrete examples which originate in classical algebraic geometry. Based on lectures given at University of Michigan, Harvard University and Seoul National University, the book is written in an accessible style and contains many examples and exercises. A novel feature of the book is a discussion of possible linearizations of actions and the variation of quotients under the change of linearization. Also includes the construction of toric varieties as torus quotients of affine spaces.
Central Hypoxic Chemoreceptors in the Ventrolateral Medulla and Caudal Hypothalamus

Even though hypoxia is known to depress the activity of many central nervous system neurons (11,12,18), CNS hypoxia increases ventilation and cardiovascular drive under some experimental and clinical conditions (1,5,8). Central hypoxia elicits the cerebral ischemic response which involves an increase in sympathetic nerve activity resulting in elevated arterial pressure, heart rate and ventricular contractility (1,8). Moreover, perfusion of hypoxic blood to the brain of the awake goat while maintaining the isolated carotid body circulation normoxic results in a tachypnea (2). In addition, hyperventilation is evoked by systemic hypoxia in the awake rat (15), cat (13), dog (3), pony (10) and goat (2) after peripheral chemoreceptor denervation. These studies suggest that central receptors exist which increase cardiorespiratory drive when stimulated by hypoxia. The recent focus of this laboratory has been to determine if hypoxia exerts a direct effect upon neurons in brain sites involved in control of the cardiovascular and respiratory systems. Our approach was to examine the in vivo and in vitro electrophysiological responses of single neurons to hypoxia (6,7,14). Our findings support the hypothesis that the inherent responses of neurons in the ventrolateral medulla (VLM) and caudal hypothalamus (CH) are involved in the coordinated response to hypoxia observed in the intact animal.
Epigenetic regulation of IFN-α2b activity in multiple myeloma by a non-hydroxamic acid HDAC inhibitor (A-423378)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA 2618 Histone deacetylases (HDACs) and histone acetyl transferases (HATs) modulate STAT1 acetylation. Acetylated STAT1 inhibits NF-κB activity leading to cell death. Since HDAC 1 and 2 respectively are overexpressed in plasma and stromal cells of myeloma patients and STAT1 is an interferon stimulated gene (ISG), we hypothesized that inhibition of HDACs may augment IFNs’ antiproliferative effects by reexpressing epigenetically silenced ISGs as well as by inhibiting NF-κB. To test this hypothesis human myeloma cell lines NCI H929, RPMI 8226 and U266 were treated with increasing concentrations (10 nM to 1000 nM) of non-hydroxamate (A-423378) HDACi as a single agent or in combination with IFN-α2b. IFN-α2b had only a marginal effect on myeloma cell viability and A-423378 inhibited myeloma cell growth with IC50 values ranging from 75-100 nM. Treatment of myeloma cell lines with IFN-α2b plus sub IC50 concentrations of A-423378 synergistically reduced the viability of NCI H929 and RPMI 8266 cell lines with combination index values of /=3x) respectively by 18 hr, whereas combination treatment induced 908 genes. Comparison of the genes induced by single vs combination treatment showed that several genes involved in IFNs antiviral response are suppressed by A-423378. However, combination treatment synergistically induced the expression of a type II tumor suppressor gene, RIG1/RARRES3 that was further confirmed by realtime RT-PCR using taqman probes. In summary, augmentation of IFNs antiproliferative effects by HDACi may be mediated in part by the synergistically induced tumor suppressor gene RIG1.
Designing & Planning Programs for Nonprofit & Government Organizations, by Edward J. Pawlak and Robert D. Vinter

As one reads this volume, one can hear the voice of an insightful, supportive coach whispering advice in the ears of beginning and advanced social work students, as well as new—and seasoned—social ...
Second order logic and first order theories of reducibility orderings

We show that the first order theories of many reducibility orderings are recursively isomorphic to second order logic on countable sets (and so to true second order arithmetic). The reduction procedure uses some initial segment results and Spector's theorem on countable ideals in the degrees to code quantification over symmetric irreflexive binary relations. This is known to be enough to obtain full second order logic. Applications to other theories are mentioned as are several to problems of definability in, and automorphisms of, the Turing degrees.
Preserving Chinese historical resources

US and Chinese institutions recently concluded a co‐operative project to microfilm more than 3,700 titles of Chinese‐language monographs published from 1932 to 1945 ‐ the years leading to and including the Sino‐Japanese War. The books were all from the collection of Fudan University in Shanghai, which also undertook the filming with support from American partners. The project had three explicit objectives: to enrich the US collection from this period, to preserve the fragile monographs, and to build capacity within Fudan University for future preservation microfilming work. While successful in meeting these objectives, the project also offers many lessons for future co‐operation.
Surface Morphology and Dynamics: Using Ab-Initio Total Energies to Make the Most of STM Data

Ab-initio total energies test typically model-dependent results of interpreting STM morphologies, and can explain what mechanisms underlie morphology change with time. Ab-initio step- and kink-formation energies for Pb(111) and Pt(111), e.g., show that the experimental results must be revised. Calculations of S-decorated Cu adclusters point to ad-Cu3S3 as an agent of S-enhanced Cu-island decay on Cu(111), in a novel “skyhook effect.”
C++ and Object-Oriented Numeric Computing for Scientists and Engineers

1. Basic Types 2. Expressions and Statements 3. Derived Types 4. Namespaces and Files 5. Classes 6. Operator Overloading 7. Templates 8. Class Inheritance 9. Exception Handling 10. Standard Libraries on Containers and Algorithms 11. Linear System Solvers References Index
The Pilgrimage of Truth Through Time : The Conception of the History of Philosophy in G.W.F. Hegel

An intimation that a very special relationship must obtain between philosophy and its own history has long haunted western thought. Equally persistent has been the premonition that the exploration of this relationship must have a profound effect, not on the historiography of philosophy alone, but on the idea of philosophy itself as well. Hegel makes vocal and brings into focus intimation and premonition alike when he writes: “… the history of philosophy because of the special nature of its subject matter (i.e. philosophy itself), is different from other histories”,*1 In what way is the history of philosophy different, in what way is this difference determined by the nature of philosophy and in what way does this difference, in turn, affect philosophy? This is the essential theme.
Revisions in real time: Spanish heritage language learners' writing processes in English and Spanish

This study presents data about the types of revisions and amount of time spent revising paragraph-length comparison essays in English and Spanish for 12 Spanish-as-a-heritage-language learners who were enrolled in a third-year Spanish course. Although most participants made revisions to both surface features and meaning in both languages, students devoted more time to meaning revisions and overall (surface and meaning) revisions when writing in English. The finding that revision behaviors were essentially the same in both English and Spanish suggests cross-linguistic transfer.
Modal-based approach to tune and enhance the frequency and dielectric bandwidth of a UHF-RFID tag antenna mounted on a dielectric substrate

A methodology to design an RFID tag antenna is presented. The tag is explicitly designed to account for changes in the dielectric constant of a thin substrate supporting the antenna. The theory of Characteristic Modes (CM), a modal-based approach, is used to study the effect of the dielectric variation on the dominant modes. The outcome of the CM analysis provides valuable guidelines to design a tag antenna that not only exhibits a large frequency bandwidth but also insensitivity to changes in the dielectric constant. Measurements and simulations show fairly good agreement. The proposed tag antenna is shown to have superior performance compared to commercially available antennas as well as antennas reported in the literature.
New techniques and results in multidimensional problems

Abstract The role of elementary decision algebra in the broad area of multidimensional problems is given, with emphasis on algorithms and computational simplification. The encouraging fact that several difficult problems can be solved in a finite number of steps via rational operations opens up unlimited scope for research into the search for more efficient algorithms. It is pointed out via a counterexample that the only existing synthesis procedure for arbitrary passive multiports with prescribed multivariable positive real matrices is incorrect. In the process, several links to the study of positivity preserving linear transformations which map square matrices into square matrices are unravelled.