cssi/SciSciGPT-SciSciNet huggingface dataset:
Serum progesterone concentration on day of embryo transfer in donor oocyte cycles

Purpose To evaluate the association between serum progesterone (P) levels on the day of embryo transfer (ET) and pregnancy rates in fresh donor IVF/ICSI cycles.
KEEPING THE CITY TOTALLY CLEAN: YELLOW FEVER AND THE POLITICS OF PREVENTION IN COLONIAL SAINT-LOUIS-DU-SÉNÉGAL, 1850–1914

This article explores the ways in which French colonial authorities met the life and death challenge represented by the re-emergence of yellow fever epidemics in Saint-Louis-du-Senegal at a time when physicians knew very little about the etiology diagnosis transmission and treatment of most infectious and parasitic diseases. The discussion focuses on changing strategies and policies designed to address yellow fever threats the attitudes and priorities of the authorities the limits of colonial medicine and the responses of people affected by sanitary measures. The article argues that because of the ignorance of the etiology and epidemiology of yellow fever policies were misdirected and did not achieve their primary goals. Even after the introduction of germ theory the gap between medical thinking and practice persisted for another decade. The African urban working class and underclass were the first victims of this state of affairs. The article also examines the conflict between the interests of public health commerce and privacy sights. (authors)
Generalized composite degradation kinetics for polymeric systems under isothermal and nonisothermal conditions

A composite degradation methodology is extended to the conversion-dependence function in order to explain the importance of multiple reaction mechanisms which might be considered to be involved in degradation processes. Based on two elementary reaction mechanisms, a specific form of the model equation is derived, which is capable of describing various types of degradation behavior showing sigmoidal rate as well as deceleratory rate. The conversion-dependence function is derived to be independent of the Arrhenius-type reaction constant or temperature, and thus the kinetic parameters are determined by analytic methods that have been developed for isothermal and dynamic-heating experiments without any modification or additional assumptions. The developed model equation is tested by predicting the isothermal master curve of polyether-ether-ketone (PEEK), which is used as a model system in this study. The activation energies of the model system are analyzed using comparable methods for isothermal and dynamic experiments, which compare favorably in terms of the activation energy as a function of conversion. The resulting model equation, based on the kinetic parameters determined by isothermal experiments, can accurately predict both isothermal and dynamic-heating thermogravimetry utilizing the same constants and identical reaction mechanisms without additional assumption.
Cell‐free translation of Drosophila imaginal disc mRNA

Total RNA derived from the imaginal discs of Drosophila melanogaster was translated in vitro, and the polypeptide products electrophoresed on two-dimensional gels. In agreement with previously published examinations of imaginal disc protein synthesis and content, we can detect no reproducible differences in abundant mRNA populations between different disc types (foreleg and wing). Differences can be found, however, between imaginal discs and other tissues. We also present evidence for a nonuniformly distributed wing disc mRNA.
Radiologic image compression-a review

The objective of radiologic image compression is to reduce the data volume of and to achieve a low bit rate in the digital representation of radiologic images without perceived loss of image quality. However, the demand for transmission bandwidth and storage space in the digital radiology environment, especially picture archiving and communication systems (PACS) and teleradiology, and the proliferating use of various imaging modalities, such as magnetic resonance imaging, computed tomography, ultrasonography, nuclear medicine, computed radiography, and digital subtraction angiography, continue to outstrip the capabilities of existing technologies. The availability of lossy coding techniques for clinical diagnoses further implicates many complex legal and regulatory issues. This paper reviews the recent progress of lossless and lossy radiologic image compression and presents the legal challenges of using lossy compression of medical records. To do so, we first describe the fundamental concepts of radiologic imaging and digitization. Then, we examine current compression technology in the field of medical imaging and discuss important regulatory policies and legal questions facing the use of compression in this field. We conclude with a summary of future challenges and research directions. >
Slipped-Strand Mispairing Can Function as a Phase Variation Mechanism in Escherichia coli

Slipped-strand mispairing (SSM) has not been identified as a mechanism of phase variation in Escherichia coli. Using a reporter gene, we show that sequences that cause phase variation by SSM in Haemophilus influenzae also lead to phase variation when introduced onto the chromosome of E. coli, and the frequencies of switching are in the biologically relevant range. Thus, the absence of SSM-mediated phase variation in E. coli does not appear to be due to a mechanistic constraint.
Benefits of Classical Biological Control for Managing Invasive Plants

As a result of the rapid expansion in international travel and trade over the past few decades, invasive plants have become a problem of global proportions. Plant invasions threaten the existence of endangered species and the integrity of ecosystems, and their ravages cost national economies tens of billions of dollars every year. Strategies for managing the threats posed by plant invasions involve three main tactics: prevention, eradication, and control. The effectiveness of prevention, involving enactment of legislation to prohibit the entry and spread of noxious alien plants, has been questioned. Eradication of all but the smallest, most localized weed infestations generally is not regarded as economically feasible. Conventional weed control techniques, such as mechanical and chemical controls, because they are expensive, energy and labor intensive, and require repeated application, are impractical for managing widespread plant invasions in ecologically fragile conservation areas or low-value habitat, ...
Patterns of change in endoneurial capillary permeability and vascular space during Wallerian degeneration

In degenerating frog sciatic nerves an in situ perfusion technique was used to measure the permeability coefficient-surface area product (PA) of endoneurial capillaries to [14C]sucrose, and the endoneurial vascular space (V). Both PA and V started to increase after the 3rd day of degeneration. The increase in PA peaked around the 14th day of degeneration and then declined to reach near normal levels at 6 weeks post-transection. V increased until about the end of the 3rd week of degeneration and then declined to near normal levels at 6 weeks after transection. The delayed increase in capillary permeability may reflect an adaptive reorganization of endoneurial capillary structure and function in response to altered conditions of the endoneurial microenvironment, and it is suggested that this permeability increase is induced by breakdown products of axons or chemical signals from Schwann cells enveloping transected axons. Fluid extravasation from these leaking capillaries is probably responsible for the endoneurial oedema observed in Wallerian degeneration. The recovery of endoneurial capillary tone to near-normal levels at 6 weeks after transection leads to the intriguing conclusion that healthy nerve fibers are not essential for the maintenance of normal endoneurial capillary permeability.
Coherent pressure fluctuations observed at two sites on the deep sea floor

Pressure fluctuations from two sites on the deep sea floor separated by a distance of 32 km were found to be partially coherent at frequencies between .001 Hz and .015 Hz. The pressure fluctuations in this range are caused by surface gravity waves which are of sufficiently long wavelength that significant coherence exists. No coherence is detected at lower frequencies because temperature fluctuations disturb the reference in the pressure gauge, while at higher frequencies the surface gravity wave induced pressure fluctuations are sharply attenuated through the ocean. The real part of the coherency as a function of frequency resembles a Jo Bessel function of argument kr (r is the distance between the sites and k is the magnitude of the wavenumber as determined by the surface gravity wave dispersion relation). The imaginary part of the complex coherency is smaller than the real part over most of the surface gravity wave band. The coherency is well modeled if the surface gravity wave field is assumed to be isotropic, but other models for the directional spectrum which require a very broad distribution in direction of propagation fit equally well. Narrow beam width models fit the data poorly.
The Psychology of the Ouija Board

We live in an age of games. It is a time when our most personal actions are acknowledged as “games people play”, when our highest elected officials unfold their “economic game plans”, and when our academic and business colleagues exhort us “to play the game” for our professional success.
Mass Spectrometry-Based Quantitative O-GlcNAcomic Analysis

The dynamic co- and post-translational modification (PTM) of proteins, O-linked β-D-N-acetylglucosamine modification (O-GlcNAcylation) of serine/threonine residues is critical in many cellular processes, contributing to multiple physiological and pathological events. The term "O-GlcNAcome" refers to not only the complete set of proteins that undergo O-GlcNAcylation but also the O-GlcNAc status at individual residues, as well as the dynamics of O-GlcNAcylation in response to various stimuli. O-GlcNAcomic analyses have been a challenge for many years. In this chapter, we describe a recently developed approach for the identification and quantification of O-GlcNAc proteins/peptides from complex samples.
Identification of Susceptibility Loci for Cutaneous Squamous Cell Carcinoma

We report a genome-wide association study of cutaneous squamous cell carcinoma conducted among non-Hispanic white members of the Kaiser Permanente Northern California health care system. The study includes a genome-wide screen of 61,457 members (6,891 cases and 54,566 controls) genotyped on the Affymetrix Axiom European array and a replication phase involving an independent set of 6,410 additional members (810 cases and 5,600 controls). Combined analysis of screening and replication phases identified 10 loci containing single-nucleotide polymorphisms (SNPs) with P -values −8 . Six loci contain genes in the pigmentation pathway; SNPs at these loci appear to modulate squamous cell carcinoma risk independently of the pigmentation phenotypes. Another locus contains HLA class II genes studied in relation to elevated squamous cell carcinoma risk following immunosuppression. SNPs at the remaining three loci include an intronic SNP in FOXP1 at locus 3p13, an intergenic SNP at 3q28 near TP63 , and an intergenic SNP at 9p22 near BNC2 . These findings provide insights into the genetic factors accounting for inherited squamous cell carcinoma susceptibility.
Effects of 5-Br-deoxyuridine and 5-F-deoxyuridine on nucleic acid metabolism by rabbit bone marrow cells.

SummaryThe effects of 5-Br-deoxyuridine and 5-F-deoxyuridine on thymidine-2-C14, formate-C14, and P32 incorporation into rabbit marrow DNA in vitro were studied. 5-Br-deoxyuridine competitively inhibits incorporation of thymidine-2-C14 into rabbit marrow DNA, and is apparently used in lieu of thymidine for DNA biosynthesis. The bone marrow is quite sensitive to the action of 5-Br-deoxyuridine. 5-F-deoxyuridine does not appreciably affect incorporation of thymidine-2-C14 or P32 into marrow DNA or formate-C14 into RNA but greatly inhibits utilization of labeled formate for DNA synthesis indicating an interference with thymidine formation.
Behavioral Responses of the Spear-Marked Black Moth, Rheumaptera hastata, to a Female-Produced Sex Pheromone

A sex pheromone was detected by laboratory and field bioassays in “calling” females of Rheumaptera hastata (L.). Male behavior is described in response to pheromone produced by 2-9-day-old live females and to extracts of female abdominal tips. Males that were 3-10 days old displayed mating behavior, with maximum response recorded from 5-day-old males. Mating behavior of this moth is similar to other Lepidoptera in more southern latitudes even though the flight season occurs during June when 20-22 h of daylight are common in northern latitudes.
Physical Chemistry of Lipoids. IV. Influence of Narcotics on the Salt-binding Capacity of Lecithin

Direct reactions between lipoids and narcotics were missed in previous studies of viscosimetry1 and interferometry.2 In view of the biological importance of lipoids, one must therefore assume that narcotics influence reactions of lipoids with other substances. Nervous excitation is explained by Nernst3 by changes of ion concentrations occurring at the surface of membranes. Experimental proof of the important role of lipoids in artificial polarizable membranes has recently been given.4 The importance of lipoids in narcosis5 has been widely assumed. Nevertheless, no data are available that connect the changes of ion concentration on the cell surface with the lipoids. Former experiments6 on the salt-binding capacity of lecithin were therefore continued, and the influence of narcotics was examined. The lecithin sols made from egg-lecithin (extra pure Merck, Germany) were either emulsions or were prepared by the method of Keeser7 (pouring small amounts of boiling alcoholic lecithin solutions into boiling disti...
The Level of Salivary Secretory Immunoglobulin A and Lysozyme in Infants with Atopic Dermatitis

Objective To study the levels of salivary secretory immunoglobulin A(sIgA) and lysozyme and its clinical significance in infants with acute atopic dermatitis(AD).Methods The levels of sIgA and lysozyme were assayed by radio-immunoassay and turbidimetry in 40 patiens with AD and 20 healthy controls.The total IgE in serum were analyzed by allergy screen automatic allergy screening system.Results ①The levels of sIgA and lysozyme and the positive rate of total IgE in serum were significantly higher in AD patients than those in healthy controls(P0.01).②There was significant correlation between the levels of sIgA or lysozyme and SCORAD score(P0.01),and the levels of sIgA in positive total IgE group were significantly higher than those in negative group in AD(P0.01).Conclusion Our study suggests that the levels of salivary secretory IgA and lysozyme may be increased in acute atopic dermatitis,which plays an important role in anti-infection and eliminate allergens.
An Output-Sensitive Algorithm for Computing Weighted α-Complexes.

An α-complex is a subcomplex of the Delaunay triangulation of a point set P ⊂ R that is topologically equivalent to the union of balls of radius α centered at the points of P . In this paper, we give an output-sensitive algorithm to compute α-complexes of n-point sets in constant dimensions, whose running time is O(f log n log αs ), where s is the smallest pairwise distance and f is the number of simplices in the cα-complex for a constant c. The algorithm is based on a refinement of a recent algorithm for computing the full Delaunay triangulation of P . We also extend the algorithm to work with weighted points provided the weights are appropriately bounded. The new analysis, which may be of independent interest, bounds the number of intersections of k-faces of a Voronoi diagram with (d− k)-faces of the Voronoi diagram of a carefully constructed superset.
Nanoscale Imaging with Soft X-Ray Lasers

This paper describes recent advances in full field aerial soft x-ray (SXR) laser microscopes. It also shows these microscopes can be readily configured into a differential holographic microscopy (DHM) geometry to acquire image plane holograms from which amplitude and phase of the object wave are obtained. The ability to quantitatively determine phase is critical at SXR wavelengths when the absorption contrast is low.
Inhibition of Growth and Aflatoxin Production of Aspergillus flavus by Lactobacillus Species

A mixture of Lactobacillus species from a commercial silage inoculum reduced mold growth and inhibited aflatoxin production by Aspergillus flavus subsp. parasiticus . Actively growing Lactobacillus spp. cells totally inhibited germination of mold spores. Culture supernatant broth from the mixture of strains inhibited mold growth but did not destroy mold spore viability. Some mold spores were observed microscopically to have germinated and produced short nonbranching germ tubes; then growth ceased. While the pH of the culture broth and supernatant were about 4.0, acidification of nonfermented broth to pH 4.0 with HCl and lactic acid did not cause a similar inhibition of spore germination. The mixture of Lactobacillus species growing in a dialysis sack inhibited aflatoxin production by the A. flavus culture growing outside of the sack in broth, whereas mold growth was not affected. The pH values outside of the dialysis sack in the control and the treatments were similar (6 to 7) throughout the incubation period. When a dialysis sack with a molecular weight cutoff (MWCO) of 1,000 was used, there was little inhibition of aflatoxin B1 production, but with MWCOs of 6,000 to 8,000 and 12,000 to 14,000 aflatoxin production was greatly inhibited. In mixed culture experiments, levels of aflatoxin B1 and G1 were depressed compared to the control (monoculture). Mold growth in this case was also reduced compared to the monoculture system. Purified isolates of Lactobacillus from the commercial mixture had a slight effect on mold growth and aflatoxin production, but supernatant liquid of one isolate was quite inhibitory to production of aflatoxins B1 and G1, without affecting mold growth.
What is Reading Religiously

To suggest that an activity called ‘religious reading’ is possible, or is a concept worth taking seriously, is itself a risk that inspires all sorts of presuppositions and prejudices. Objections to the value of discussing such a venture can range from the conservative argument that the issue has already been decided (religious reading is what believers do with their sacred texts) to the liberal assertion (any ‘existential’ reading of any text that addresses matters of ‘ultimate concern’ is religious) to the radical rejection (in a world in which religious belief is no longer plausible it is pointless to speak of religious readings unless to describe objectively the phenomenon of what believers do) to the deconstructive position that in a world without authoritative ‘presence’ religious discourse, including reading, must be redefined along with all other modes.2 I would like to play with the possibility of religious reading precisely because it appears to be such a pointless and undecidable issue. Its very perceived gratuitousness hints at the likelihood that a most significant complex of irresolutions and anxieties is hidden in the dismissal of the question.
CSV: Image quality assessment based on color, structure, and visual system

Abstract This paper presents a full-reference image quality estimator based on color, structure, and visual system characteristics denoted as CSV. In contrast to the majority of existing methods, we quantify perceptual color degradations rather than absolute pixel-wise changes. We use the CIEDE2000, color difference formulation to quantify low-level color degradations and the Earth Mover's Distance between color name probability vectors to measure significant color degradations. In addition to the perceptual color difference, CSV also contains structural and perceptual differences. Structural feature maps are obtained by mean subtraction and divisive normalization, and perceptual feature maps are obtained from contrast sensitivity formulations of retinal ganglion cells. The proposed quality estimator CSV is tested on the LIVE, the Multiply Distorted LIVE, and the TID 2013 databases, and it is always among the top two performing quality estimators in terms of at least ranking, monotonic behavior or linearity.
Stream Microbial Ecology in a Changing Environment

Abstract Preamble This contribution deals broadly with how the ecology of stream microbes will be studied, integrated, and affected by a new conceptual backdrop for streams and new physical conditions in streams. Some of the anticipated changes in the topic of stream microbial ecology (SME) will be driven by an altered scientific capacity, which includes both improved conceptual models and methods. Some of the anticipated changes in SME will be driven by a host of currently occurring, or forecast changes in physical, chemical, and biotic attributes of stream networks, along with changes in external drivers with temperature and flow among the most obvious. Ideally, the improvements in scientific capacity will outpace alterations in stream network attributes such that understanding, confidence, and management will be proactive rather than reactive. Part of the challenge in projecting how stream microbes will be understood within the broader context of stream function is recognizing when established drivers of microbial structure and function are operating outside the previously observed range, and/or when novel drivers exert a significant influence on stream microbes. Our ability to address this question is greatly strengthened by both conceptual and methodological advances. Microbial communities living in streams have always been recognized as key players in organic matter decomposition and cycling of nutrients—nitrogen in particular. To a large extent, we understand the major factors affecting which microbial groups occur or carry out particular processes across various stream types. Looking forward, there will be major improvements due to advances in conceptual frameworks and methodological capacity. Concurrently, the biophysicochemical context for stream microbes has been, and will continue to change at unprecedented rates and thus, the “rules of the game” are changing perhaps as fast as our capacity to discover them. Conceptual advances include better representation of the diversity of microbes and the processes they carry out, as well as better integration of multiple spatial and temporal scales in models of stream networks. Methodology addressing microbial identity and phenotypic capacity has exploded to the point that it is almost routine to have a species list for micro- as well as macro-organisms.
OCT1 genetic variants are associated with postoperative morphine-related adverse effects in children

Aim: Large interindividual variability in morphine pharmacokinetics (PK) could contribute to variability in morphine analgesia and adverse events. Respiratory depression (RD) and postoperative nausea and vomiting (PONV) are significant adverse drug response of intravenous morphine in the perioperative setting limiting its efficacy in achieving adequate surgical pain relief. OCT1 is a transporter in the liver that transports morphine from the bloodstream into hepatocytes. Earlier we reported association of genetic polymorphisms in OCT1 with morphine PK, and lower morphine clearance in Caucasian children as compared with African–American (AA) children. The aim of this study is to identify the association between common OCT1 genotypes affecting morphine’s PK and clinically important postoperative morphine-related adverse outcomes. Methods: After obtaining institutional review board (IRB) approval and informed consents, 311 children ages 6–15 years, American Society of Anesthesiologists’ physical status 1 or ...
Platelet-Derived Growth Factor as an Antidepressant Treatment Selection Biomarker: Higher Levels Selectively Predict Better Outcomes with Bupropion-SSRI Combination

Background Platelet derived growth factor is integral to maintenance of blood brain barrier, increases in response to blood brain barrier disruption, and may reflect neuroinflammation. Based on previous reports of better outcomes with dopaminergic antidepressants in depressed patients with elevated inflammatory biomarkers, we hypothesize that elevated peripheral platelet derived growth factor levels can serve as a powerful biomarker for selecting dopaminergic antidepressants. Methods Platelet derived growth factor, basic fibroblast growth factor, and granulocyte colony stimulating factor were measured as part of Bioplex Pro human cytokine 27-plex kit in participants of the Combining Medications to Enhance Depression Outcomes trial who provided baseline plasma (n=166) and were treated with either bupropion-plus-escitalopram, escitalopram-plus-placebo, or venlafaxine-plus-mirtazapine. Differential changes in overall symptom severity and anhedonia as well as side effects were tested with a treatment-arm-by-biomarker interaction in mixed model analyses. Effect of biomarkers with significant interaction was calculated in subsequent analyses stratified by treatment arm. Results There was a significant treatment-arm-by-platelet derived growth factor interaction for depression severity (P=.03) and anhedonia (P=.008) but not for side effects (P=.44). Higher baseline platelet derived growth factor level was associated with greater reduction in depression severity (effect size=0.71, P=.015) and anhedonia (effect size=0.66, P=.02) in the bupropion- selective serotonin reuptake inhibitor but not the other two treatment arms. There was no significant treatment-arm-by-biomarker interaction for both depression severity and side effects with the other two biomarkers. Conclusion As compared with selective serotonin reuptake inhibitor monotherapy or venlafaxine-plus-mirtazapine, bupropion-plus-escitalopram selectively improves anhedonia, which in turn results in improved overall depression severity in depressed patients with elevated platelet derived growth factor levels.
Afterword: New Institutional, Inhabited Institutional, and a Cultural-Organizational Approach to Studying Elites and Higher Education

The afterword reflects on this volume’s chapters using several approaches attentive to culture and organization. It first sketches the now-classic new institutional approach to studying the origin and diffusion of elite practices and identities in educational settings. It then lays out several of the critiques that sociologists level against new institutionalism – in particular, its emphasis on organizational convergence and its general neglect of power and interests. Binder proposes to use the relatively new “inhabited institutions” mode of organizational analysis for a more sophisticated understanding of the fit between broad-scale logics governing higher education and organizational action at the level of regions, nations, and individual university campuses. Finally, she lays out the elements of a cultural-organizational approach to studying individual universities’ distinctive effects on shaping elites.
Obituary: Thomas A. McMahon (1943-99)

Thomas A. McMahon: Biomechanist who discovered fundamental principles of biological structure and function.
Current Paradigms in Powder Processing

The theoretical work and model experiments on sintering and hot pressing have provided a basis to qualitatively interpret much of the behavior observed in these processes as practiced in the technology. The data base and the modeling, however, are inadequate to quantitatively predict the kinetics of materials responses for these processes (including grain growth) for most systems of interest. In this paper the authors present their biases in a review of the paradigms (current “axioms”) in the field, citing the literature sources which support our biases. Several paradigms have changed significantly in the past several years. As a consequence, new directions for the course of productive research are needed; we present our best guesses for them. We also give emphasis to some earlier theoretical and experimental work which we regard as important, the significance of which seems to us not to have been duly appreciated.
ON THE USER INTERFACE OF COMPUTING SOFTWARE

In principle, computing softwares are created for the problem-solving users and for the convenience of such users. In practice, software designers often neglect or fall short of this goal. In this article, some common weaknesses in existing software, particularly in the area of user interface, will be discussed. Reasons and possible remedies for the weaknesses are suggested.
A day with Elmer

Judith Harries suggests organising a special ‘Elmer's Day’ to celebrate the importance of making friends and settling differences. Try her ideas for drama games which will help to develop social awareness.
The Role of Sex Differences in Inflammation and Autoimmune Diseases

Abstract Inflammation is an immune defense mechanism against injury or infection, and plays an integral role in both the innate and adaptive immune responses. Humans exhibit strong sex differences in immune responses and inflammation, with women having an enhanced immune reaction as compared to males. Sex hormones and genetics play a role in mediating various components of the immune system and contribute significantly to the sex differences observed in the immune response and inflammation. A sustained immune response characterized by the production of autoantibodies or effector immune cells that react to host tissues or endogenous peptide results in autoimmune diseases. Eighty percent of autoimmune disease patients are female. The enhanced immune reactivity in females may predispose women to the development of autoimmune disease and is implicated in the sexual dimorphism of autoimmune disease prevalence. Studies have examined the influence of female and male sex hormones, as well as genetic differences in both sexes that are associated with enhanced risk or prevalence of autoimmune diseases. Investigations have also examined the effect of sex hormone therapy as treatment options for autoimmune diseases. A new area of interest is the contribution of genes on sex and nonsex chromosomes in autoimmune disease prevalence and progression. A better understanding of the mechanisms that underlie development and progression of autoimmune diseases, as well as the mediators of sex differences in these disorders may result in the development of novel therapeutic strategies to better manage these unique disorders.
DNA Methylation in Neuronal Development and Disease

DNA methylation is an epigenetic modification that spatially and temporally regulates gene expression and has essential roles in controlling neuronal development and function. DNA methylation is generally associated with heterochromatin and repression of gene transcription. Methylated cytosine residues can also undergo demethylation by ten-eleven translocation (TET) enzymes, resulting in 5-hydroxymethylation and its downstream derivatives. Once thought of as an intermediary in the demethylation process, 5-hmC has been found to be a unique and stable epigenetic mark. 5-hmC is more highly enriched in mammalian brains than in other somatic cells, indicating its critical roles in the central nervous system. Unlike methylation, hydroxymethylation is usually associated with euchromatin and gene activation. Much progress has been made in the past few decades in defining the roles of methylation and hydroxymethylation, and their molecular machinery in the brain and nervous system. In this chapter, we provide a comprehensive review of the roles of methylation and hydroxymethylation in brain development, functions and their dysregulation in brain disorders. First, we discuss the current understanding of these epigenetic marks in normal neuronal development as well as brain function. DNA methylation and hydroxymethylation have also been implicated in the development and progression of neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases. We discuss consistencies and inconsistencies of the available data in human, mouse and in vitro studies that link methylation and hydroxymethylation to neurodegeneration. Finally, we explore the potential of these neuronal epigenetic marks and their molecular machinery to provide novel therapeutic targets in neurodegenerative diseases.
EPITAXIAL GROWTH OF β-SILICON CARBIDE

ABSTRACT Epitaxial growth of β-SiC on solution grown β-SiC substrates was studied. The structure and morphology of the epitaxial deposit was dependent on temperature and vapor composition. The etching rate in hydrogen, and the vapor growth kinetics were determined. Electroluminescence and diode characteristics of p/n junctions were also investigated.
Murine models for familial pancreatic cancer: Histopathology, latency and drug sensitivity among cancers of Palb2, Brca1 and Brca2 mutant mouse strains

Alterations of the PALB2 tumor suppressor gene have been identified in familial breast, ovarian and pancreatic cancer cases. PALB2 cooperates with BRCA1/2 proteins through physical interaction in initiation of homologous recombination, in maintenance of genome integrity following DNA double-strand breaks. To determine if the role of PALB2 as a linker between BRCA1 and BRCA2 is critical for BRCA1/2-mediated tumor suppression, we generated Palb2 mouse pancreatic cancer models and compared tumor latencies, phenotypes and drug responses with previously generated Brca1/2 pancreatic cancer models. For development of Palb2 pancreatic cancer, we crossed conditional Palb2 null mouse with mice carrying the KrasG12D; p53R270H; Pdx1-Cre (KPC) constructs, and these animals were observed for pancreatic tumor development. Individual deletion of Palb2, Brca1 or Brca2 genes in pancreas per se using Pdx1-Cre was insufficient to cause tumors, but it reduced pancreata size. Concurrent expression of mutant KrasG12D and p53R270H, with tumor suppressor inactivated strains in Palb2-KPC, Brca1-KPC or Brca2-KPC, accelerated pancreatic ductal adenocarcinoma (PDAC) development. Moreover, most Brca1-KPC and some Palb2-KPC animals developed mucinous cystic neoplasms with PDAC, while Brca2-KPC and KPC animals did not. 26% of Palb2-KPC mice developed MCNs in pancreata, which resemble closely the Brca1 deficient tumors. However, the remaining 74% of Palb2-KPC animals developed PDACs without any cysts like Brca2 deficient tumors. In addition, the number of ADM lesions and immune cells infiltrations (CD3+ and F/480+) were significantly increased in Brca1-KPC tumors, but not in Brca2-KPC tumors. Interestingly, the level of ADM lesions and infiltration of CD3+ or F/480+ cells in Palb2-KPC tumors were intermediate between Brca1-KPC and Brca2-KPC tumors. As expected, disruption of Palb2 and Brca1/2 sensitized tumor cells to DNA damaging agents in vitro and in vivo. Altogether, Palb2-KPC PDAC exhibited features observed in both Brca1-KPC and Brca2-KPC tumors, which could be due to its role, as a linker between Brca1 and Brca2.
Synergistic Combination of Oncolytic Virotherapy and Immunotherapy for Glioma.

Purpose: We hypothesized that the combination of a local stimulus for activating tumor-specific T cells and an anti-immunosuppressant would improve treatment of gliomas. Virally encoded IL15Rα-IL15 as the T-cell activating stimulus and a prostaglandin synthesis inhibitor as the anti-immunosuppressant were combined with adoptive transfer of tumor-specific T cells. Experimental Design: Two oncolytic poxviruses, vvDD vaccinia virus and myxoma virus, were each engineered to express the fusion protein IL15Rα-IL15 and a fluorescent protein. Viral gene expression (YFP or tdTomato Red) was confirmed in the murine glioma GL261 in vitro and in vivo. GL261 tumors in immunocompetent C57BL/6J mice were treated with vvDD-IL15Rα-YFP vaccinia virus or vMyx-IL15Rα-tdTr combined with other treatments, including vaccination with GARC-1 peptide (a neoantigen for GL261), rapamycin, celecoxib, and adoptive T-cell therapy. Results: vvDD-IL15Rα-YFP and vMyx-IL15Rα-tdTr each infected and killed GL261 cells in vitro. In vivo, NK cells and CD8+ T cells were increased in the tumor due to the expression of IL15Rα-IL15. Each component of a combination treatment contributed to prolonging survival: an oncolytic virus, the IL15Rα-IL15 expressed by the virus, a source of T cells (whether by prevaccination or adoptive transfer), and prostaglandin inhibition all synergized to produce elimination of gliomas in a majority of mice. vvDD-IL15Rα-YFP occasionally caused ventriculitis-meningitis, but vMyx-IL15Rα-tdTr was safe and effective, causing a strong infiltration of tumor-specific T cells and eliminating gliomas in 83% of treated mice. Conclusions: IL15Rα-IL15–armed oncolytic poxviruses provide potent antitumor effects against brain tumors when combined with adoptive T-cell therapy, rapamycin, and celecoxib.
Gaussian Prepivoting for Finite Population Causal Inference

In finite population causal inference exact randomization tests can be constructed for sharp null hypotheses, i.e. hypotheses which fully impute the missing potential outcomes. Oftentimes inference is instead desired for the weak null that the sample average of the treatment effects takes on a particular value while leaving the subject-specific treatment effects unspecified. Without proper care, tests valid for sharp null hypotheses may be anti-conservative should only the weak null hold, creating the risk of misinterpretation when randomization tests are deployed in practice. We develop a general framework for unifying modes of inference for sharp and weak nulls, wherein a single procedure simultaneously delivers exact inference for sharp nulls and asymptotically valid inference for weak nulls. To do this, we employ randomization tests based upon prepivoted test statistics, wherein a test statistic is first transformed by a suitably constructed cumulative distribution function and its randomization distribution assuming the sharp null is then enumerated. For a large class of commonly employed test statistics, we show that prepivoting may be accomplished by employing the push-forward of a sample-based Gaussian measure based upon a suitably constructed covariance estimator. In essence, the approach enumerates the randomization distribution (assuming the sharp null) of a P-value for a large-sample test known to be valid under the weak null, and uses the resulting randomization distribution to perform inference. The versatility of the method is demonstrated through a host of examples, including rerandomized designs and regression-adjusted estimators in completely randomized designs.
Validation and Uncertainty Quantification for Two-Phase Natural Circulation Flows Using TRACE Code

The work presents validation of the TRAC/RELAP Advanced Computational Engine (TRACE) code for natural circulation two-phase flow in a vertical annulus. Natural circulation experiments were recently...
Impact of Race-Ethnic and Economic Disparities on Rates of Vascular Dementia in the National Inpatient Sample Database from 2006-2014

Background We have previously reported regional differences in the rates of vascular dementia (VD) in the United States (US), with the West having lower rates of VD diagnosis found in the Healthcare Cost and Utilization Project Nationwide Inpatient Sample (NIS) Database. We aimed to determine if these regional differences were associated with race-ethnic disparities in economic status or prevalence of the stroke risk factors hypertension, diabetes, and hyperlipidemia. Methods A sampling of the NIS database from 2006-2014 was analyzed using ICD-9 codes (290.40, 290.41, and 290.43) to identify patients admitted with primary or secondary VD diagnoses. Multivariable logistic regression was used to identify significant associations between ethnic groups, stroke risk factors and income. Results The NIS sample included 69,273,455 patients with median age of 53 (interquartile range 27 - 72), 55% female and 34% non-Caucasian. The mean VD primary and secondary diagnosis were 0.03% and 0.21% respectively. Black/African Americans had the highest odds of being admitted with a primary VD code [odds ratio (OR) 1.307, confidence interval (CI) 1.248-1.369] or admitted with VD as a secondary diagnosis code [OR 1.998, CI 1.968-2.03]. Black/African Americans admitted with VD as a primary diagnosis were the only group to have increased odds of having all 3 stroke risk factors, hypertension [OR 1.856, CI 1.705-2.019], diabetes [OR 1.166, CI 1.072-1.268], and hyperlipidemia [OR 1.164, CI 1.062-1.276]. Also, Black/African Americans admitted with VD as a secondary diagnosis had increased odds for the most stroke risk factors of the ethnic groups, including diabetes [OR 1.187, CI 1.155-1.22] and hypertension [OR 1.04, CI 1.012-1.068]. Caucasians were the only group less likely to be admitted with a primary VD diagnosis with increasing income [$25,001-30,000, OR 0.782; $30,001-35,000, OR 0.75; $35,000 or greater, OR 0.77; p-value Conclusion We demonstrate how healthcare disparities in race-ethnicity can influence the frequency of VD diagnosis in the US. This highlights the need for investigating the impact of healthcare disparities across the spectrum of cerebrovascular disease.
ACL Growth With Age in Pediatric Patients: An MRI Study.

Background There is limited knowledge of morphologic changes of the anterior cruciate ligament (ACL) during childhood. The purpose of the study is to describe normal ACL growth in pediatric patients. Methods We performed retrospective review of patients under 19 years of age with at least 2 serial magnetic resonance imaging (MRI) examinations of the same knee without ACL tear. The parameters measured included length of the ACL, width of the ACL in sagittal and coronal planes, physeal status, ACL-tibial inclination angle, Notch Width Index, ACL tibial attachment width and midpoint, and anterior to posterior length and height of the tibial epiphysis. Pearson correlation coefficients were calculated to determine the strength of correlation of each parameter relative to age. Growth curves were calculated for individual parameters, producing a predictive model for growth of the ACL over time. Results One hundred forty-seven patients (365 MRIs) were included. The average age at initial MRI was 12.2 years (range: 1.2 to 18.4 y). The Pearson correlation coefficient for each parameter was statistically significant relative to age. Younger patients had more oblique, anteriorly attached ACLs. Three distinct phases of growth were observed: patients age 1.5 to 5.75 years average 2.25 mm of growth per year; patients aged 6 to 11.5 average 1.46 mm of growth per year; growth slows at age 11.75, stopping by 18.5 years. The growth model for ACL sagittal width increased 0.45 mm/y from age 1.5 to 14.5 after which it plateaus, whereas coronal width increased 0.22 mm/y from age 1.5 to 18.75. Conclusions In the pediatric patient, the ACL grows in length and width in a predictable manner until age 18. This model aids clinicians in predicting normal ACL parameters for anatomic reconstruction procedures in the skeletally immature patient. Level of evidence Level IV.
Laboratory Tests for COVID-19: A Review of Peer-Reviewed Publications and Implications for Clinical Use

Diagnostic tests for the coronavirus infection 2019 (COVID-19) are critical for prompt diagnosis, treatment and isolation to break the cycle of transmission. A positive real-time reverse-transcriptase polymerase chain reaction (RT-PCR), in conjunction with clinical and epidemiologic data, is the current standard for diagnosis, but several challenges still exist. Serological assays help to understand epidemiology better and to evaluate vaccine responses but they are unreliable for diagnosis in the acute phase of illness or assuming protective immunity. Serology is gaining attention, mainly because of convalescent plasma gaining importance as treatment for clinically worsening COVID-19 patients. We provide a narrative review of peer-reviewed research studies on RT-PCR, serology and antigen immune-assays for COVID-19, briefly describe their lab methods and discuss their limitations for clinical practice.
Irreversible Langevin samplers and variance reduction: a large deviations approach

In order to sample from a given target distribution (often of Gibbs type), the Monte Carlo Markov chain method consists of constructing an ergodic Markov process whose invariant measure is the target distribution. By sampling the Markov process one can then compute, approximately, expectations of observables with respect to the target distribution. Often the Markov processes used in practice are time-reversible (i.e. they satisfy detailed balance), but our main goal here is to assess and quantify how the addition of a non-reversible part to the process can be used to improve the sampling properties. We focus on the diffusion setting (overdamped Langevin equations) where the drift consists of a gradient vector field as well as another drift which breaks the reversibility of the process but is chosen to preserve the Gibbs measure. In this paper we use the large deviation rate function for the empirical measure as a tool to analyze the speed of convergence to the invariant measure. We show that the addition of an irreversible drift leads to a larger rate function and it strictly improves the speed of convergence of ergodic average for (generic smooth) observables. We also deduce from this result that the asymptotic variance decreases under the addition of the irreversible drift and we give an explicit characterization of the observables whose variance is not reduced reduced, in terms of a nonlinear Poisson equation. Our theoretical results are illustrated and supplemented by numerical simulations.
High-Accuracy Unambiguous Localization Using Spectrally Sparse Code-Modulated Signals

Open-loop coherent distributed antenna arrays require that the localization error between the nodes is λ/15 or less to achieve 90% coherent gain with high probability, leading to ranging accuracies on the order of cm for beamforming at microwave frequencies. We present a ranging system using two code-modulated tones generated on separate transceivers in software-defined radio for unambiguous high-accuracy localization of nodes in distributed antenna arrays. The best peak-to-sidelobe level was -0.89 dB with the code-modulated waveform compared to -0.11 dB for a standard two-tone waveform, each with a frequency separation of 10 MHz. This increased suppression, though minimal in a traditional radar detection sense, is significant for cooperative ranging between nodes in a distributed array. The code-modulated two-tone waveform achieved a range accuracy below 3 cm in a wireless ranging setup.
Etiology and management of hypertension in patients with cancer

The pathophysiology of hypertension and cancer are intertwined. Hypertension has been associated with an increased likelihood of developing certain cancers and with higher cancer-related mortality. Moreover, various anticancer therapies have been reported to cause new elevated blood pressure or worsening of previously well-controlled hypertension. Hypertension is a well-established risk factor for the development of cardiovascular disease, which is rapidly emerging as one of the leading causes of death and disability in patients with cancer. In this review, we discuss the relationship between hypertension and cancer and the role that hypertension plays in exacerbating the risk for anthracycline- and trastuzumab-induced cardiomyopathy. We then review the common cancer therapies that have been associated with the development of hypertension, including VEGF inhibitors, small molecule tyrosine kinase inhibitors, proteasome inhibitors, alkylating agents, glucocorticoids, and immunosuppressive agents. When available, we present strategies for blood pressure management for each drug class. Finally, we discuss blood pressure goals for patients with cancer and strategies for assessment and management. It is of utmost importance to maintain optimal blood pressure control in the oncologic patient to reduce the risk of chemotherapy-induced cardiotoxicity and to decrease the risk of long-term cardiovascular disease.