cssi/SciSciGPT-SciSciNet huggingface dataset:
Normal Aging and Alzheimer's Disease

Neuronal loss does not occur in the entorhinal cortex (EC) or the superior temporal sulcus region (STS) in cognitively intact elderly persons within the four decades assessed. It is found that there is a selective and very dramatic loss of neurons in the EC even at the mildest stages of dementia in Alzheimer's disease (AD), likely even at a presymptomatic point. This alteration almost certainly contributes to the memory impairment that characterizes the earliest clinical phases of this type of dementia. At later points of the disease, when the illness is perhaps more clinically apparent, the STS association cortex also undergoes neuronal loss as clinical symptoms of a more advanced cognitive impairment become prominent. The observations suggest that no significant neuronal loss takes place in the EC in cognitively intact elderly individuals, at least in the age range of about 60 to about 90. These findings support a model where AD and normal aging are not part of a continuum, and can be differentiated both anatomically and clinically.
Pediatric clinical pharmacology and therapeutics

Children younger than 15 years old account for 28% of the population worldwide and about one quarter of the US population. As one must undergo the developmental trajectory of childhood to reach adulthood, any discussion of clinical pharmacology would be incomplete without inclusion of how development, the most dynamic period of human life, influences drug disposition and action and creates unique therapeutic scenarios that are not seen in adults. Development, despite being a continuum of physiologic events that culminate in maturity, is often arbitrarily divided into the stages of infancy, childhood, adolescence, and even early adulthood. Across this period of time, organ size and function change, as do body composition, protein expression, and cellular function. Some cellular components are active during early development and subsequently lose function with age, and vice versa . Some tissues may be more sensitive to pharmacologic effects early in life, whereas function may decline later in life. As these developmental changes in function and form occur, their implications must be considered, both with respect to the clinical pharmacology of drugs and to their appropriate place in pediatric pharmacotherapy.
Affect, persuasion, and communication processes

Publisher Summary This chapter primarily focuses on how emotion affects the processing of persuasive messages in the mind of the receiver. The chapter addresses a number of conceptually “gray areas” surrounding the use and definitions of emotional appeals and affect. Emotion plays a crucial role in the formation of attitudes. Thus, understanding the role of affect in the structure of attitudes can result in a better conceptualization of how affect may be effectively used in promoting and resisting persuasion. Attitudes consisting of three interrelated components: affect, cognition, and behavior. The cognitive component represents the thoughts, beliefs, and judgments about an attitude object, whereas the affective component represents the feelings associated with the object. The behavioral component of an attitude consists of predispositions towards action with regard to the attitude object. Several models of attitude change are also discussed in the chapter, establishing a better understanding of how emotional appeals are processed, and with what kinds of consequences.
Bone Metastases and Skeletal-Related Events in Medullary Thyroid Carcinoma

Context: Bone metastases (BM) can lead to devastating skeletal-related events (SREs) in cancer patients. Data regarding medullary thyroid carcinoma (MTC) with BM are lacking. Objective: We evaluated the natural history of BM and SREs in MTC patients identified by a cancer center tumor registry. Setting: The study was conducted at a tertiary cancer center. Patients and Main Outcome Measures: We retrospectively reviewed the charts of MTC patients with BM who received care from 1991 to 2014 to characterize BM and SREs. Results: Of 1008 MTC patients treated, 188 were confirmed to have BM (19%), of whom 89% (168 of 188) had nonosseous distant metastases. Median time from MTC to BM diagnosis was 30.9 months (range 0–533 mo); 25% (45 of 180) had BM identified within 3 months of MTC diagnosis. Median follow-up after detecting BM was 1.6 years (range 0–23.2 y). Most patients (77%) had six or more BM lesions, most often affecting the spine (92%) and pelvis (69%). Many patients (90 of 188, 48%) experienced one or mo...
Organelles – understanding noise and heterogeneity in cell biology at an intermediate scale

Many studies over the years have shown that non-genetic mechanisms for producing cell-to-cell variation can lead to highly variable behaviors across genetically identical populations of cells. Most work to date has focused on gene expression noise as the primary source of phenotypic heterogeneity, yet other sources may also contribute. In this Commentary, we explore organelle-level heterogeneity as a potential secondary source of cellular 'noise' that contributes to phenotypic heterogeneity. We explore mechanisms for generating organelle heterogeneity and present evidence of functional links between organelle morphology and cellular behavior. Given the many instances in which molecular-level heterogeneity has been linked to phenotypic heterogeneity, we posit that organelle heterogeneity may similarly contribute to overall phenotypic heterogeneity and underline the importance of studying organelle heterogeneity to develop a more comprehensive understanding of phenotypic heterogeneity. Finally, we conclude with a discussion of the medical challenges associated with phenotypic heterogeneity and outline how improved methods for characterizing and controlling this heterogeneity may lead to improved therapeutic strategies and outcomes for patients.
Glucocorticoid receptor binding to chromatin is selectively controlled by the coregulator Hic-5 and chromatin remodeling enzymes

The steroid hormone-activated glucocorticoid receptor (GR) regulates cellular stress pathways by binding to genomic regulatory elements of target genes and recruiting coregulator proteins to remodel chromatin and regulate transcription complex assembly. The coregulator hydrogen peroxide-inducible clone 5 (Hic-5) is required for glucocorticoid (GC) regulation of some genes but not others and blocks the regulation of a third gene set by inhibiting GR binding. How Hic-5 exerts these gene-specific effects and specifically how it blocks GR binding to some genes but not others is unclear. Here we show that site-specific blocking of GR binding is due to gene-specific requirements for ATP-dependent chromatin remodeling enzymes. By depletion of 11 different chromatin remodelers, we found that ATPases chromodomain helicase DNA-binding protein 9 (CHD9) and Brahma homologue (BRM, a product of the SMARCA2 gene) are required for GC-regulated expression of the blocked genes but not for other GC-regulated genes. Furthermore, CHD9 and BRM were required for GR occupancy and chromatin remodeling at GR-binding regions associated with blocked genes but not at GR-binding regions associated with other GC-regulated genes. Hic-5 selectively inhibits GR interaction with CHD9 and BRM, thereby blocking chromatin remodeling and robust GR binding at GR-binding sites associated with blocked genes. Thus, Hic-5 regulates GR binding site selection by a novel mechanism, exploiting gene-specific requirements for chromatin remodeling enzymes to selectively influence DNA occupancy and gene regulation by a transcription factor.
Molecular Systematics, Microbial Ecology and Single Cell Analysis

Molecular approaches in taxonomy and systematics are providing a unifying framework for understanding the phylogenetic relationships of diverse biological species. The methods rely on comparison of nucleic acid or amino acid sequences, which can serve as yardsticks for measuring evolutionary divergence. Direct sequence analysis can largely circumvent problems inherent in phenotypic comparisons of widely divergent taxa. Macromolecular sequence information is particularly useful in situations where directly comparable phenotypic properties are scarce or difficult to assess. Additionally, macromolecular sequence data bases are valuable resources for determining the phylogenetic affiliations of previously unstudied or uncharacterized organisms. In particular, current understanding of the evolutionary relationships of microbial species has been greatly advanced through molecular phylogenetic comparisons of small subunit ribosomal RNA (rRNA) sequences.
Gender Differences in Human Neuropsychological Function

Scientific studies of sex differences in cognitive abilities have been stimulated by a long history of popular interest in psychological differences between men and women. According to Anastasi, when Samuel Johnson was asked whether men or women were more intelligent, he replied by asking, “Which man, which woman?” (p. 453, Anastasi, 1958). Johnson’s reply highlights the fact that for a very large number of cognitive capacities (e.g., vocabulary, verbal reasoning, the ability to recognize an object from incomplete parts), no consistent sex differences exist. For other cognitive characteristics, the average difference between sexes is very small compared to within-gender variations. As Anastasi (1958) says, “Owing to the large extent of individual differences within any one group as contrasted to the relatively small difference between group averages, an individual’s membership in a given group furnishes little or no information about his status in most traits” (p. 453).
Nature is logical, because logic is natural

Nature is logical because elemental logic has been implicitly abstracted from natural processes. The symbolic representation of logical statements shows a “form” that logicians have long believed to guarantee the truth of statements. This is most applicable to deductive logic in which the conclusions are implicit in the premise. In contrast, inductive logic cannot be formalized and is inferred from many specific observations to make a general hypothesis, whose validity can be tested. This is the essence of the scientific experimental method and presupposes the uniformity of nature. Inductive logic is the product of our intelligence and capacity to observe, describe, and encode natural phenomena in our brain, a view that philosophers and logicians have traditionally dismissed. Drawing valid conclusions is a natural process that can be observed in preverbal humans and in animals.
Long-term postoperative effects of administration of allogeneic blood products in 104 dogs with hemangiosarcoma.

OBJECTIVE To determine the influence of administering allogeneic blood products (ABP) on the progression of hemangiosarcoma in dogs. STUDY DESIGN Multi-institutional, retrospective study. SAMPLE POPULATION One hundred four dogs with hemangiosarcoma that survived until postoperative discharge from the hospital. METHODS Medical records of dogs that had been operated on for hemoangiosarcoma were reviewed for signalment, presence of a hemoabdomen, presence of metastatic disease, and whether the dog had received chemotherapy or Yunnan Baiyao. Data that were collected were compared between dogs that received perioperative ABP and those that did not. Disease-free interval was compared between groups. The Kaplan-Meier method was used to obtain univariate descriptive statistics for time to clinical decline. A multivariable Cox regression model was used to analyze association or effect of potential predictor variables. RESULTS The median disease-free interval (DFI) was shorter in the 67 dogs that received a blood transfusion (76 days; range, 1-836) than in the 37 dogs that did not receive a blood transfusion (120 days; range, 38-916). According to the multivariable Cox regression model, administration of blood products (P = .04) and the presence of gross metastatic disease at the time of surgery (P < .01) shortened the DFI, whereas administration of Yunnan Baiyao (P = .01) prolonged the DFI. CONCLUSION Allogeneic blood product administration was associated with a shorter disease-free interval in this population. However, we could not demonstrate the association between blood products and shorter DFI because of confounding factors. CLINICAL SIGNIFICANCE Dogs that receive ABP at the time of surgical therapy for hemangiosarcoma may have accelerated disease progression compared with dogs that do not receive ABP.
Psychometric Properties of the Simons Simplex Collection Sleep Interview.

BACKGROUND AND PURPOSE An estimated 40%-80% of children with autism spectrum disorders (ASD) have sleep problems. The Simons Simplex Collection Sleep Interview (SSCSI) is a parent-report questionnaire assessing bedtime and nighttime sleep problems and daytime function. The present study evaluated the factorial model of the SSCSI that best characterizes children aged 4-18 years with ASD. METHODS Exploratory factor analysis was performed using principal component analysis and promax rotation, beginning with 16 items and ending with 10 items. RESULTS Exploratory factor analysis concluded with ten dichotomous items, plus ageand regular sleep duration, in three factors: nighttime problems, daytime problems, andsleep duration problems. The analysis was performed on the full sample, and onprepubertal (4-8-years), pubertal (9-13-years), and postpubertal (14-18-years) subgroups. CONCLUSION Further refinement, including confirmatory factor analysis, test-retest reliability, and convergent validity testing, is needed.
P-030 Low nihss M1 occlusion stroke: preliminary single-center outcomes of medical management versus thrombectomy

Background and purpose The clinical constellation of mild acute stroke symptoms and M1 occlusion occurs not infrequently. Whereas thrombectomy is clearly beneficial for ELVO with NIHSS ≥8, which is predominantly embolic, milder presentation suggests chronic etiology, namely intracranial atherosclerotic disease (ICAD), for which thrombectomy has not been shown an effective treatment. This retrospective study reports the discharge outcomes of medical management versus mechanical thrombectomy in a retrospective cohort of patients with low NIHSS M1 occlusion stroke. Methods We performed a retrospective chart review of patients presenting to our institution between 2013 and 2018 with hyperacute M1 occlusion and NIHSS ≤9. Patients were divided into three groups by presenting NIHSS: very low (VLPN; NIHSS ≤4), intermediate low (ILPN; 4 9), and upper low (ULPN; NIHSS=9). The primary outcome was difference in clinical neurologic status (NIHSS) between discharge and presentation, dichotomized into Stable/Improved (≤0) or Worsened (>0). Groupwise difference in change in NIHSS from presentation to discharge was assessed for statistical significance nonparametrically (Kruskal-Wallis). Results Twenty-nine patients (17 male, 12 female) presented with hyperacute M1 occlusion stroke and NIHSSS ≤9. The VLN group showed higher rate of diabetes (p=0.043) and a trend toward higher prevalence of alcohol use (p=0.183); the groups were otherwise comparable. At discharge, 8/8 VLPN patients (all medically managed) showed stable/improved NIHSS. Of the ILPN patients, 10 were stable/improved and 7 were worsened; of the 8 managed medically, 4 were neurologically stable/improved at discharged versus 4 worsened; and of the 9 who received thrombectomy, 6 were stable/improved versus 3 worsened. 4/4 of the ULPN patients received thrombectomy; at discharge 3 were stable or improved, whereas 1 was worsened. The difference in change in NIHSS between the three groups was not statistically significant (p=0.847), although it trended towards significance when stratifying by treatment (figure 1; p=0.156). Conclusion These preliminary data suggest that patients with M1 occlusion stroke and very low presentation NIHSS ( Disclosures A. Nasiri: None. J. Burns-Benggon: None. P. Kim: 6; C; AUR GE Radiology Research Academic Fellowship. M. Gezalian: None. U. Oyoyo: None. D. Hoss: None. J. Jacobson: 4; C; Genelux, Inc.
Abstract LB-048: WRN helicase is a synthetic lethal target in microsatellite unstable cancers

Microsatellite instability (MSI), a class of genetic hypermutability that arises from impaired DNA mismatch repair (MMR), contributes to the development of many malignancies including colon, endometrial, gastric, and ovarian cancers. While immune checkpoint blockade (ICB) has been an effective therapy for many patients with MSI cancers, numerous patients with MSI malignancies do not respond to ICB or the use of these agents are limited by their toxicity. Hence, there is still a pressing need to develop further therapies against MSI cancers. One approach to develop novel therapeutics is to leverage synthetic lethality, a phenomenon whereby the simultaneous occurrence of two or more genetic events lead to cell death but one event alone does not. DNA repair processes represent attractive synthetic lethal targets since many cancers exhibit an impaired DNA repair pathway, which can lead these cancers to become dependent on specific repair proteins. The success of poly (ADP ribose) polymerase (PARP) inhibitors in homologous recombination-deficient cancers highlights the potential of this approach. Hypothesizing that other DNA repair defects would give rise to alternative synthetic lethal relationships, we asked if there are specific dependencies in MSI cancers. Here, we analyzed data from large-scale CRISPR/Cas9 and RNA interference (RNAi) functional genomic screens and found that the RecQ DNA helicase WRN was selectively essential in MSI models in vitro and in vivo, but dispensable in microsatellite stable models. WRN silencing induced double-strand DNA breaks, activated a DNA-damage response, and promoted apoptosis and cell cycle arrest preferentially in MSI models. MSI cancer models specifically required WRN’s helicase activity, but not its exonuclease activity. These findings expose WRN as a synthetic lethal vulnerability and promising drug target for MSI cancers. Citation Format: Edmond M. Chan, Tsukasa Shibue, James McFarland, Benjamin Gaeta, Francisca Vazquez, Adam J. Bass. WRN helicase is a synthetic lethal target in microsatellite unstable cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-048.
Dialogue as the Conditio Humana : a Critical Account of Dmitri Nikulin’s Theory of the Dialogical

Dmitri Nikulin is one of the few contemporary philosophers to have devoted books to the topic of dialogue and the dialogical self, especially in the last fifteen years. Yet his work on dialogue and the dialogical has received scant attention by philosophers, and this neglect has hurt the ongoing development of contemporary philosophical work on dialogicality. I want to address this lacuna in contemporary philosophical scholarship on dialogicality and suggest that, although Nikulin’s account is no doubt insightful and thought-provoking, it is problematic for two main reasons: first, his account fails to recognize the proper relationship between dialogue and agency; and second, his enumeration of the necessary and sufficient conditions for dialogue contains conceptual inconsistencies.
The effects of data entry structure on patients' perceptions of information quality in Health Information Exchange (HIE).

Abstract Background and objective To exchange patient health information using Health Information Exchange (HIE) projects, such information first should be collected thoroughly using an appropriate data entry interface that reinforces information quality (IQ). Assessment of the given data interface based on its structure level may give us a better understanding of patients’ attitudes toward information-sharing efforts. The main objective of this study is to examine the effects of data structure on perceptions and attitudes of patients toward the quality of health information that may be shared through HIE networks. Materials and Methods Eight experiments were conducted to examine the impact of different design of information collection interfaces (structured vs. unstructured) to record two types of health information (sensitive vs. non-sensitive) that can be used for two types of sharing purposes (health care vs. marketing). Results Results show that the degree of data entry structure can significantly influence patients’ perceptions of completeness, accuracy, psychological risk, accessibility of data, concise representation, and understandability of health information. Discussion There is a connection between data entry interface design and patients’ perceptions of the quality of health information used in HIE networks, which in turn, could lead to the development of best practices in interface design and data collection techniques. This may also improve interactions between patients and healthcare entities, enhance patients’ attitudes toward data collection procedures and HIE, and help healthcare providers use complete and accurate databases. Conclusions We propose that healthcare professionals can tailor data entry interfaces based on the sensitivity of medical data and the purpose of information exchange.
Establishing a Novel High-Throughput Conditioning-Free HSC Transplant Model in Zebrafish

Hematopoietic stem cell (HSC) transplantation is a widely successful treatment, but the risk of mortality remains. Preclinical modeling is critical to uncover the biological components that underlie poor patient outcomes. Zebrafish is a vertebrate animal with high genetic and cellular conservation with human hematopoiesis with many advantages to discover regulators of HSC transplant biology, such as high fecundity and short generation time. We developed a novel HSC transplant model using bloodless runx1 W84X mutant zebrafish which are devoid of endogenous HSCs. Most embryos die 8-12 days post fertilization (dpf) due to the absence of definitive hematopoiesis. We hypothesized that the empty HSC niche and lack of an immune system would prevent graft rejection, making robust HSC engraftment possible. We transplanted donor marrow ubiquitously expressing green fluorescent protein (ubi:GFP) via intravascular injection into runx1 homozygous mutants and heterozygotes at 2dpf. Sham-injected and uninjected embryos served as negative controls. We transplanted an average of 100-200 recipients per experimental day. Survival was significantly improved in transplanted runx1 mutants, with 64% surviving in the transplanted cohort compared to 5% in the sham-injected controls, suggesting HSC transplantation likely supplied these fish with a functional hematopoietic compartment critical for survival. Chimerism was quantified by flow cytometry 8 weeks post-transplant. Successful engraftment was defined as >5% GFP+ myeloid cells. Over 99% of animals meeting this criterion also showed robust multi-lineage engraftment. Over 70% of runx1 mutant recipients were engrafted compared to only 3% of the runx1 heterozygotes. The myeloid chimerism of engrafted mutant fish was 84% (+/-25%), while the engrafted heterozygous control had only 21% myeloid chimerism. Transplanted fish remain robustly engrafted >6 months post-transplant. The runx1 mutants supported HSC self-renewal, as the GFP+ marrow cells from primary recipients were able to robustly engraft secondary runx1 mutant hosts. We also demonstrated that competitive transplantation in runx1 mutants can be used to measure HSC frequency, a critical feature needed to functionally and quantitatively assess HSC potential following genetic or pharmacological perturbations. These data demonstrate that the runx1 mutant zebrafish is an advantageous HSC transplant host that allows quantification of long-term serially-repopulating true HSCs. The advantages of our zebrafish transplant model allow the real-time visualization of stem cell trafficking and homing in a healthy, uninjured niche and the ability to perform large-scale screens to identify drugs that modify engraftment. This will provide unprecedented insight into both the donor and host factors needed for robust HSC engraftment that will be helpful in improving human HSC graft outcomes.
Diagnostic Accuracy of Noninvasive Tests to Detect Advanced Hepatic Fibrosis in Patients With Hepatitis C and End-Stage Renal Disease.

Background & Aims For patients with liver disease from hepatitis C virus (HCV) infection complicated by end-stage renal disease (ESRD), it is important to assess liver fibrosis before kidney transplantation. We evaluated the accuracy of non-invasive tests to identify advanced hepatic fibrosis in patients with HCV and ESRD. Methods In a retrospective study, we collected data on ratio of aspartate aminotransferase:alanine aminotransferase (AST:ALT), AST platelet ratio index (APRI), FIB-4 score, fibrosis index score, and King's score from 139 patients with ESRD and HCV infection (mean age, 52.8 y; 76.3% male; 86.4% African American; 45.3% with increased level of ALT). Results were compared with findings from histologic analyses of biopsies (reference standard). The primary outcome was detection of advanced fibrosis, defined as either bridging fibrosis or cirrhosis. Area under the receiver operating characteristic (AUROC) curves were constructed and optimal cutoff values were determined for each test. Sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy were calculated. We repeated the analysis with stratification for normal levels of ALT (≤ 35 U/L for men and ≤ 25 u/L for women) and increased levels of ALT. Results FIB-4 scores identified patients with advanced fibrosis with an AUROC of 0.71 (95% CI, 0.61–0.80), the King's score with an AUROC of 0.69 (95% CI, 0.58–0.80), and the APRI with and AUROC of 0.68 (95% CI, 0.59–0.79). The accuracy of these tests increased when they were used to analyze patients with increased levels of ALT. All tests produced inaccurate results when they were used to assess patients with normal levels of AST and ALT. Conclusions In patients with ESRD and HCV infection, FIB-4 scores, King's scores, and the APRI identify those with advanced fibrosis with AUROC values ranging from 0.68–0.71. Accuracy increased modestly when patients with increased levels of ALT were tested, but the tests produced inaccurate results for patients with a normal level of ALT.
Assessing the “Education Debt”: Teach For America and the Problem of Attrition

With this paper, I explore the impact of teacher attrition on Teach For America’s (TFA) ability to produce more long-term, systemic educational change. I do so via my application of critical race theory and Gloria Ladson-Billings’ concept of the “education debt” to TFA’s consistently high rates of attrition. I begin with a general discussion of long-term educational change, paying particular attention to how and why teacher attrition matters. Next, I present the four components of Ladson-Billings’ (2006a) conception of the “education debt,” after which I explore just one factor that I believe may prevent the realization of TFA’s goal of ending educational inequity (teacher attrition) in both practical and moral terms. Using critical race theory as an additional level of analysis that is consistent with Ladson-Billings “education debt” framework, I conclude that TFA’s concrete materiality falls short of its intention to end educational inequity, especially concerning the longevity of its recruits. This, I contend, suggests the need for educational resources to be equitably redistributed, in part, via high quality educators for our most under-served youth populations, including those currently taught by TFA.
5.523 – Carbon Nanotubes: Applications for In Situ Implant Sensors

In this chapter, the use of multiwalled carbon nanotubes (MWCNTs) as sensors for healthy bone growth are discussed. MWCNTs are cytocompatible with osteoblasts (bone-forming cells) and enhance osteoblast calcium deposition, and thus, bone formation. Moreover, MWCNTs have been grown out of nanopores of anodized titanium (MWCNT-Ti), which has a surface layer of titanium oxide (a popular chemistry for orthopedic implants) to serve as a novel in situ orthopedic implant sensor. The electrochemical responses of MWCNT-Ti have been investigated in an attempt to ascertain if MWCNT-Ti can serve as novel in situ sensors for bone formation. MWCNT-Ti has been subjected to a ferri/ferrocyanide redox couple and its electrochemical behavior measured. Cyclic voltammograms (CVs) have demonstrated enhanced redox potentials of the MWCNT-Ti compared to Ti alone. These redox signals have been superior to that obtained from bare Ti, which does not sense either oxidation or reduction peaks in CV. Moreover, the redox reactions of MWCNT-Ti have been tested in a solution of extracellular bone components synthesized by osteoblasts in vitro. It has been found that MWCNT-Ti also exhibited well-defined and persistent CV, similar to the ferri/ferrocyanide redox reaction. The observed higher electrodic performance and electrocatalytic activity the MWCNT-Ti senses compared to bare Ti are likely because of the fact that MWCNTs enhance direct electron transfer and facilitate double-layer effects, leading to a strong redox signal. These collective results may encourage further study and modification of MWCNT-Ti to sense new bone growth in situ next to implants and perhaps to monitor other events (such as infection and/or scar tissue formation) to improve the current clinical diagnosis of orthopedic implant success or failure.
The Developmental Decrease in REM Sleep: The Role of Transmitters and Electrical Coupling

A NUMBER OF RECENT REVIEWS PROVIDE DETAILED DESCRIPTIONS OF THE ORGANIZATION OF THE NEUROLOGIC SUBSTRATES CONTROLLING SLEEP-WAKE systems.1–6 The reader is also referred to an extensive consideration of rapid eye movement (REM) sleep.7 Our recent mini-review focused on developmental events related to the decrease in REM sleep, including its relationship to other developmental changes, the role of blood flow, some factors that may influence its progress, and its potential role in brain development.8 Briefly, the part of the brain controlling sleep-wake states and most responsible for inducing REM sleep is the reticular activating system (RAS), especially its cholinergic component. The RAS triggers changes in state mainly via its ascending projections to the intralaminar thalamus (ILT) to modulate thalamocortical systems in both waking and REM sleep, while simultaneously modulating REM sleep and postural muscle tone via its descending projections to the pontomedullary reticular formation. Since that review, a more complete survey of the transmitter systems that affect these neurons has been completed, and the role of electrical coupling as a novel mechanism in sleep-wake control has been discovered. We will describe the organization of sleep-wake control systems in the adult and then deal with development.
2 λ switch

We demonstrate an elastic multi-wavelength selective switch with up to two wavelength switching capability per crosspoint. We fabricated the switch in a silicon photonics foundry and demonstrated a 17 nm tuning range for ring resonators, with a mean path loss of 2.43 dB. This is a 70% reduction in path loss as compared to previous generations, and we demonstrate a high-speed pulse-amplitude-modulation-4 transmission at 111 Gbps through different paths of the switch.
Deep Convolutional Mixture Density Network for Inverse Design of Layered Photonic Structures

Machine learning (ML) techniques, such as neural networks, have emerged as powerful tools for the inverse design of nanophotonic structures. However, this innovative approach suffers some limitatio...
Experiences of School Nurses Caring for Newly Arrived Immigrant and Refugee Children

Newly arrived immigrant and refugee children are faced with significant physical and mental health issues and often rely on school nurses for care and connection to healthcare. The purpose of this ...
Exploring the Relationship of Variant Degrees of National Economic Freedom to the Ethical Profiles of Millennial Business Students in Eight Countries

This research explores the relationship of variant degrees of a country’s economic freedom to the ethical profiles of millennial business students, specifically an individual’s personal value orien...
On the photo-evaporation, dust polarization, and kinematics of two nebulae in Sh2-236

In the work presented here, the impact of magnetic field on the dynamical evolution of cometary globules Sim 129 and Sim 130 in Sh2-236 H\,II region and the ionized gas streaming out of their surfaces is investigated. The magnetic field morphology in the region associated with these globules is inferred using optical polarization measurements with the Sampurnanand Telescope at ARIES. The nebular emission is probed through radio continuum mapping at 1.4~GHz with the archival National Radio Astronomy Observatory (NRAO) very large array (VLA) Sky Survey (NVSS) data. The correlation of these measurements suggest that the photoevaporated gas from the surfaces of Sim 129 and Sim 130 is accumulated in clouds and starts streaming along the magnetic field lines. The $\rm ^{12}CO$ (J=1-0) molecular line observations are performed towards NGC\,1893 from 14-m single dish radio telescope in Taeduk Radio Astronomy Observatory (TRAO). The velocity dispersion in $\rm ^{12}CO$ (J=1-0) molecular line and the dispersion in polarization angles are used in Davis-Chandrasekhar-Fermi formulation to estimate the magnetic field strength towards two sim nebulae. The average value of field strength is found to be $\sim$60$\mu$G with uncertainty of 0.5 times the estimated value.
A global pandemic in the time of viral memes: COVID-19 vaccine misinformation and disinformation on TikTok.

Misinformation and disinformation regarding COVID-19 and vaccination against it may be contributing to vaccine hesitancy. Social media outlets have reportedly made efforts to limit false informatio...
The potential for qualitative triangulation to mitigate investigative negligence

Identifying investigative negligence as the prevalent cause for wrongful convictions in the United States is supported in the academic literature. Most of that research has concluded with a call fo...
Valuation of Large Variable Annuity Portfolios: Monte Carlo Simulation and Benchmark Datasets

Metamodeling techniques have recently been proposed to address the computational issues related to the valuation of large portfolios of variable annuity contracts. However, it is extremely difficult, if not impossible, for researchers to obtain real datasets from insurance companies in order to test their metamodeling techniques on such real datasets and publish the results in academic journals. Even if a researcher can obtain real datasets from insurance companies, it is difficult for the re- searcher to share the datasets with the public at large. To facilitate the development and dissemination of research related to the efficient valuation of large variable annuity portfolios, this paper creates a large synthetic portfolio of variable annuity contracts based on the properties of real portfolios of variable annuities and implements a Monte Carlo simulation engine for valuing the synthetic portfolio. In addition, this paper develops benchmark datasets of fair market values and Greeks, which are important quantities for managing the financial risks associated with variable annuities. The resulting datasets provide researchers with a common basis for testing and comparing the performance of various metamodeling techniques.
I am Afraid of Lateral Column Lengthening. Should I Be

Lateral column lengthening has long been used in conjunction with other soft tissue and bony procedures to correct the midforefoot abduction seen in class B progressive collapsing foot deformity. The effectiveness of this osteotomy to restore the physiologic shape of the foot has been used by foot and ankle surgeons around the world to provide functional improvement for patients suffering from this disease. The overall low complication rates, low nonunion rates, and improved radiographic and functional outcomes provided by lateral column lengthening make this a valuable option for the treatment of class B progressive collapsing foot deformity.
The partial molal volume and compressibility of Tris and Tris–HCl in water and 0.725 m NaCl as a function of temperature

Abstract The apparent molal volumes and compressibilities of Tris and Tris–HCl have been determined in water (5–45 °C) and 0.725 m NaCl (5–25 °C). The changes in the volume (Δ V ) and compressibility (Δ κ ) for the dissociation of Tris–H + Tris - H + = Tris + H + as functions of temperature in water and 0.725 m NaCl have been determined from these measurements. The values of Δ V and Δ κ have been used to determine the effect of pressure on the dissociation constant for Tris–H + ( K P / K 0 ). ln ( K P / K 0 ) = - ∆ V / ( R T ) P + 0 .5∆ k / ( R T ) P 2 These results will be useful in the calibration of pH systems making in-situ measurements at high pressure in seawater. In 0.725 m NaCl at 5 °C and a pressure of 2000 bar, the dissociation constant is reduced by 29%.
Glycoproteins Specified by Human Cytomegalovirus

Human cytomegalovirus (CMV) belongs to the herpesviruses, a group of large DNA viruses. CMV virions contain a DNA core, an icosahedral capsid, a poorly defined tegument or matrix, and an outer membrane designated as the envelope. This review focuses on the viral glycoproteins at the surface of the envelope and the infected cell. Inasmuch as the envelope is the outermost structure of the virion and contains the viral glycoproteins, it seems reasonable to attribute to them the function of adsorption and penetration of virions into the host cell. Studies with monoclonal antibodies to CMV have shown that infected cells contain at least four antigenically distinct glycoproteins (Pereira et al., 1982b; Pereira and Hoffman, 1984a). At the present time, there is little information on their structure and fucntion, their synthesis and processing, or the location of the glycoprotein gene templates on the DNA. I will summarize the data currently available and will describe in depth recently completed studies from my laboratory using monoclonal antibodies for characterizing the immunological and electrophoretic properties of CMV glycoproteins.
VAMP8 is a vesicle SNARE that regulates mucin secretion in airway goblet cells

Mucin secretion is an innate defence mechanism, which is noxiously upregulated in obstructive lung diseases (e.g. chronic obstructive pulmonary disease (COPD), cystic fibrosis and asthma). Mucin granule exocytosis is regulated by specific protein complexes, but the SNARE exocytotic core has not been defined in airway goblet cells. In this study, we identify VAMP8 as one of the SNAREs regulating mucin granule exocytosis. VAMP8 mRNA was present in human airway and lung epithelial cells, and deep-sequencing and expression analyses of airway epithelial cells revealed that VAMP8 transcripts were expressed at 10 times higher levels than other VAMP mRNAs. In human airway epithelial cell cultures and freshly excised tissues, VAMP8 immunolocalised mainly to goblet cell mucin granules. The function of VAMP8 in airway mucin secretion was tested by RNA interference techniques. Both VAMP8 short interfering RNAs (siRNAs) and short hairpin RNAs (shRNAs) reduced mucin secretion induced by PAR agonists, neutrophil elastase and ATP in two airway epithelial cell culture models. Notably, basal (non-agonist elicited) mucin secretion was also reduced in these experiments. VAMP8 knockdown was also effective in decreasing mucin secretion in airway epithelial cell cultures with induced mucous metaplasia/mucin hypersecretion. Unlike VAMP8 silencing, knockdown of VAMP2 or VAMP3 did not affect mucin secretion. Importantly, in VAMP8 knock-out (KO) mice with IL-13-induced mucous metaplasia, mucin content in the bronchoalveolar lavage (BAL) and ATP-stimulated mucin secretion in the trachea were reduced compared to WT-matched littermates. Our data indicate that VAMP8 is an essential SNARE in airway mucin granule exocytosis. Reduction of VAMP8 activity/expression may provide a novel therapeutic target to ameliorate airway mucus obstruction in lung diseases.
Molar mass, surface tension, and droplet growth kinetics of marine organics from measurements of CCN activity

[1] The CCN-relevant properties and droplet growth kinetics are determined for marine organic matter isolated from seawater collected near the Georgia coast. The organic matter is substantially less CCN active than (NH4)2SO4, but droplet growth kinetics are similar. Kohler Theory Analysis (KTA) is used to determine the average organic molar masses of two samples, which are 4370 ± 24% and 4340 ± 18% kg kmol−1. KTA is used to infer surface tension depression, which is in excellent agreement with direct measurements. For the first time it is shown that direct measurements of surface tension are relevant for CCN activation, and this study highlights the power of KTA.
Novel ethanol-in-fluorocarbon microemulsions for topical genetic immunization.

Purpose. Traditionally, vaccines have been administered by needle injection. Topical immunization through the intact skin with either protein- or DNA-based vaccines has attracted much attention recently. We sought to enhance the immune responses induced by DNA-based vaccines after topical application by developing novel ethanol-in-fluorocarbon (E/F) microemulsion systems to aid in the delivery of plasmid DNA (pDNA).
Regulation of cell movement is mediated by stretch-activated calcium channels

Intracellular calcium regulates many of the molecular processes that are essential for cell movement. It is required for the production of actomyosin-based contractile forces, the regulation of the structure and dynamics of the actin cytoskeletons, and the formation and disassembly of cell-substratum adhesions. Calcium also serves as a second messenger in many biochemical signal-transduction pathways. However, despite the pivotal role of calcium in motile processes, it is not clear how calcium regulates overall cell movement. Here we show that transient increases in intracellular calcium, [Ca2+]i, during the locomotion of fish epithelial keratocytes, occur more frequently in cells that become temporarily 'stuck' to the substratum or when subjected to mechanical stretching. We find that calcium transients arise from the activation of stretch-activated calcium channels, which triggers an influx of extracellular calcium. In addition, the subsequent increase in [Ca2+]i is involved in detachment of the rear cell margin. Thus, we have defined a mechanism by which cells can detect and transduce mechanical forces into biochemical signals that can modulate locomotion.
Progress with Recombinant Adeno-Associated Virus Vectors for Gene Therapy of Alpha-1 Antitrypsin Deficiency

Abstract The pathway to a clinical gene therapy product often involves many changes of course and strategy before obtaining successful results. Here we outline the methodologies, both clinical and preclinical, that went into developing a gene therapy approach to the treatment of alpha-1 antitrypsin deficiency lung disease using muscle-targeted recombinant adeno-associated virus. From initial gene construct development in mouse models through multiple rounds of safety and biodistribution studies in rodents, rabbits, and nonhuman primates to ultimate human trials, this review seeks to provide insight into what clinical translation entails and could thereby inform the process for future investigators.
Minimal Surfaces, Gauss Maps, Total Curvature, Eigenvalue Estimates, and Stability

The subject matter that I wish to discuss here is one that seems particularly appropriate to this occasion. It is in fact, as will become abundantly clear, one of the many parts of differential geometry where Chern’s influence has been both fundamental and pervasive. What is more, a substantial portion of the body of recent work described here is closely related to, and in many cases directly inspired by, a single paper of Chern’s [19]—his first paper devoted to the theory of minimal surfaces.
Everyday Expertise: Land Regularization and the Conditions for Land Grabs in Petén, Guatemala:

Advocates claim that market-assisted land reform (MALR) promotes economic development and reduces poverty by improving the security of private property rights and the efficiency of land markets. However, scholars argue that MALR often benefits elites at the expense of the disadvantaged and forces intended beneficiaries to resist or make difficult compromises. Nevertheless, this critical literature largely glosses everyday processes of implementation that help this policy get traction in particular locations. This paper examines the work of regularizing (titling) land in the context of a World-Bank-funded MALR project in northern Guatemala. Specifically, the focus is on the meaning-making work of field technicians who seek to convince campesinos (peasants) to participate in this regularization project. In their recruiting efforts, these technicians creatively link neoliberal slogans, human rights narratives, and exclusionary visions of nation, race, and property. By examining how technicians elaborate know...
Peripherally inserted central catheter use in the hospitalized patient: is there a role for the hospitalist?

BACKGROUND: Peripherally-inserted central venous catheters (PICCs) are frequently used in hospitals for central intravenous access. These catheters may offer advantages over traditional central catheters with respect to ease of placement and decreased complication rates. However, hospital physicians have not traditionally been trained to place PICCs. METHODS: We trained 3 of 5 hospitalists to place PICCs in our small university-affiliated community hospital as we converted from a house physician model to a hospitalist model for inpatient care. We then looked retrospectively at the rates of all PICC and other central catheter placements as well as the number of femoral and nonfemoral catheter days for the 18-month period prior to and after the inception of the hospitalist program. RESULTS: Comparing the periods prior to and after the inception of the hospitalist program, the total number of central catheter placements doubled and the PICC rate rose from 20% to 80% of all central catheters. The rate of femoral and subclavian catheter placements decreased by approximately 50% and the rate of internal jugular catheter placement was roughly unchanged. There was also a fall in the number of femoral catheter days and a great increase in the number of total nonfemoral catheter days. The rate of catheter-related bacteremia remained low and did not appear to increase. CONCLUSIONS: PICCs may be a safe and easy alternative to centrally placed catheters for the hospital physician attempting to secure central intravenous access and may lead to a decrease in the need for more risky central venous catheter (CVC) insertions. Journal of Hospital Medicine 2009;4:E1–E4. © 2009 Society of Hospital Medicine.
2,3-Butanedione monoxime cardioplegia : Advantages over hyperkalemia in blood-perfused isolated hearts

Abstract Background . 2,3-Butanedione monoxime (BDM) has been shown to possess cardioprotective properties related to the inhibition of cross-bridge force development, the reduction of myofilament Ca 2+ sensitivity, and the attenuation of intracellular Ca 2+ transients. This study tested the hypothesis that cardiac arrest achieved with BDM would be as effective as that achieved with St. Thomas' solution (StT). Methods . Isolated rabbit hearts, studied on a blood-perfused Langendorff column, underwent 1 hour of ischemia (37°C) and 30 minutes of reperfusion. Cardioplegia was administered every 20 minutes in the form of (1) Krebs-Henseleit solution only (control), (2) 20 mmol/L of BDM, or (3) StT. Recovery of developed pressure, atrioventricular activation times, and tissue water content were measured. Results . Recovery of developed pressure for the control, BDM, and StT groups was 44% ± 3% ( p p = 0.042) and the StT group (26 ± 9 ms, p = 0.034), but not in the BDM group (14 ± 8 ms). Tissue water content after reperfusion was 80% ± 0.4%, 80% ± 0.2%, and 76% ± 1.0% ( p Conclusions . 2,3-Butanedione monoxime was as effective as StT in protecting the myocardium. Unlike StT, BDM ameliorated myocardial edema and atrioventricular conduction delay after reperfusion.