cssi/SciSciGPT-SciSciNet huggingface dataset:
Effects of Triazolam on the Perception of Sleep and Wakefulness in Insomniacs

AbstractAlthough the short-acting benzodiazepines are the most widely used hypnotics in the world, the mechanism by which they induce a sense of improved sleep remains obscure. In order to determine whether triazolam alters the perception of being asleep, we have performed auditory arousal threshold measures on chronic insomniacs during waking and sleeping at five points through the night, and then questioned them regarding their subjective experience prior to each forced arousal. As expected, triazolam 0.25 mg resulted in increased EEG or behavioral arousal thresholds 5 minutes after “lights out,” during stage 2 sleep 10 minutes after the first sleep spindle, and during spontaneous waking time. As with other benzodiazepine hypnotics, the arousal thresholds in stage 2 on active drug nights exceeded the amplitude of common commercial smoke alarms. Patients reported having been awake during the stage 4 trial in 50% of the cases after placebo, but only 8% after 0.25 mg triazolam (p < 0.02). After triazolam, ...
Topological invariants of field lines rooted to planes

Abstract Two open curves with fixed endpoints on a boundary surface can be topologically linked. However, the Gauss linkage integral applies only to closed curves and cannot measure their linkage. Here we employ the concept of relative helicity in order to define a linkage for open curves. For a magnetic field consisting of closed field lines, the magnetic helicity integral can be expressed as the sum of Gauss linkage integrals over pairs of lines. Relative helicity extends the helicity integral to volumes where field lines may cross the boundary surface. By analogy, linkages can be defined for open lines by requiring that their sum equal the relative helicity. With this definition, the linkage of two lines which extend between two parallel planes simply equals the number of turns the lines take about each other. We obtain this result by first defining a gauge-invariant, one-dimensional helicity density, i.e. the relative helicity of an infinitesimally thin plane slab. This quantity has a physical interpr...
Detection of eQTL modules mediated by activity levels of transcription factors

Motivation: Studies of gene expression quantitative trait loci (eQTL) in different organisms have shown the existence of eQTL hot spots: each being a small segment of DNA sequence that harbors the eQTL of a large number of genes. Two questions of great interest about eQTL hot spots arise: (1) which gene within the hot spot is responsible for the linkages, i.e. which gene is the quantitative trait gene (QTG)? (2) How does a QTG affect the expression levels of many genes linked to it? Answers to the first question can be offered by available biological evidence or by statistical methods. The second question is harder to address. One simple situation is that the QTG encodes a transcription factor (TF), which regulates the expression of genes linked to it. However, previous results have shown that TFs are not overrepresented in the eQTL hot spots. In this article, we consider the scenario that the propagation of genetic perturbation from a QTG to other linked genes is mediated by the TF activity. We develop a procedure to detect the eQTL modules (eQTL hot spots together with linked genes) that are compatible with this scenario. Results: We first detect 27 eQTL modules from a yeast eQTL data, and estimate TF activity profiles using the method of Yu and Li (2005). Then likelihood ratio tests (LRTs) are conducted to find 760 relationships supporting the scenario of TF activity mediation: (DNA polymorphism → cis-linked gene → TF activity → downstream linked gene). They are organized into 4 eQTL modules: an amino acid synthesis module featuring a cis-linked gene LEU2 and the mediating TF Leu3; a pheromone response module featuring a cis-linked gene GPA1 and the mediating TF Ste12; an energy-source control module featuring two cis-linked genes, GSY2 and HAP1, and the mediating TF Hap1; a mitotic exit module featuring four cis-linked genes, AMN1, CSH1, DEM1 and TOS1, and the mediating TF complex Ace2/Swi5. Gene Ontology is utilized to reveal interesting functional groups of the downstream genes in each module. Availability: Our methods are implemented in an R package: eqtl.TF, which includes source codes and relevant data. It can be freely downloaded at http://www.stat.ucla.edu/~sunwei/software.htm Abbreviations: eQTL (expression Quantitative Trait Loci); TF (Transcription Factor); QTG (Quantitative Trait Gene); SNP (Single Nucleotide Polymorphism); FDR (False Discovery Rate); SGD (Saccharomyces Genome Database); LRT (Likelihood Ratio Test). Contact: kcli@stat.ucla.edu Supplementary information: http://www.stat.ucla.edu/~sunwei/yeast_eQTL_TF/supplementary.pdf
Tracheal Mucous Velocity in Beagles After Chronic Exposure to Cigarette Smoke

Tracheal mucous velocity (TMV) was determined in eight purebred beagle dogs exposed to cigarette smoke (100 cigarettes per week) for 13.5 months, and four control dogs. By means of a mask, smoke was administered through both the mouth and nose for 1.5 hours twice daily. The TMV was measured under thiopental sodium anesthesia 24 hours after the last exposure by means of a cinebronchofiberscopic technique. There was a significant decrease in TMV in dogs exposed to cigarette smoke compared with the control animals. Lung compliance and resistance, single breath diffusing capacity, lung volumes, and arterial Po2, Pco2, and pH did not differ significantly between the two groups. We conclude that suppression of mucociliary activity associated with cigarette smoking may precede abnormalities of pulmonary function as determined by conventional methods.
Evaluation of Four Techniques for Injecting the Trochanteric Bursa of Horses

Objective: To describe the anatomic features of the equine trochanteric bursa and to evaluate 4 techniques for bursa centesis. Study Design: Prospective, randomized design. Animals: Equine cadavers (n=2) and 20 live horses. Methods: The trochanteric bursae of 2 equine cadavers were injected with latex to identify the boundaries of the bursae. Four techniques for centesis of the trochanteric bursa were evaluated by attempting to inject dye into both trochanteric bursae of 20 live horses. Techniques included injection of the bursa with the limb-bearing weight and injection with the limb nonweight bearing and supported on a block, with or without ultrasonographic guidance of the needle. Ultrasonographic guidance of the needle was performed with or without the use of a guide channel attached to the ultrasound probe. Each of the 4 techniques was used to inject 10 bursae. The region of the bursa was dissected after horses were euthanatized to determine the location of the dye. Results: The trochanteric bursa was most successfully injected with the limb positioned caudally with the foot on a block, even though topographic landmarks for centesis were more difficult to identify when the limb was in this position. The highest incidence of success was achieved when the needle was inserted using ultrasonographic guidance with the foot in a Hickman block. Conclusion: Positioning the limb caudally with the foot nonweight bearing and on a block facilitated centesis of the trochanteric bursa.
Flexible polyimide-based intracortical electrode arrays with bioactive capability

The promise of advanced neuroprosthetic systems to significantly improve the quality of life for a segment of the deaf, blind, or paralyzed population hinges on the development of an efficacious, and safe, multichannel neural interface for the central nervous system. The candidate implantable device that is to provide such an interface must exceed a host of exacting design parameters. The authors present a thin-film, polyimide-based, multichannel intracortical Bio-MEMS interface manufactured with standard planar photo-lithographic CMOS-compatible techniques on 4-in silicon wafers. The use of polyimide provides a mechanically flexible substrate which can be manipulated into unique three-dimensional designs. Polyimide also provides an ideal surface for the selective attachment of various important bioactive species onto the device in order to encourage favorable long-term reactions at the tissue-electrode interface. Structures have an integrated polyimide cable providing efficient contact points for a high-density connector. This report details in vivo and in vitro device characterization of the biological, electrical and mechanical properties of these arrays. Results suggest that these arrays could be a candidate device for long-term neural implants.
Surgical complications of laparoscopic urological surgery

Objectives To describe the incidence, identification and management of common intraoperative complications, including vascular, urological, bowel and visceral complications, of laparoscopic urological surgery.
Breeding and Recruitment Phenology of Amphibians in Missouri Oak-Hickory Forests

ABSTRACT Knowing the phenologies of species in a region helps guide management and conservation activities in breeding ponds and surrounding terrestrial habitats. We examined the phenology of pond-breeding amphibians in central Missouri oak-hickory forests. Two ponds were monitored for 4 y from 2000–2003 and five other ponds were monitored for 1 y during 2004 using drift fences with pitfall traps. We found 15 species of pond-breeding amphibians, nine of which we captured in sufficient abundance to evaluate breeding phenology. Among the nine species, breeding migrations occur from Feb. to Nov., while subsequent metamorph emigration occurred primarily from May to Oct.. Our ponds were nearly permanent, resulting in salamander-dominated communities in these oak-hickory forests. Pond-use was partitioned by species that differed in their timing of reproduction and post-metamorphic emergence. For example, breeding in the fall gives larval ringed salamanders a potential size advantage over the spring-breeding spo...
Male Sexuality and Alfred Kinsey's 0–6 Scale: Toward “A Sound Understanding of the Realities of Sex”

Using a 0-6 scale, Alfred Kinsey demonstrated that the complexity of human sexuality could best be represented on a continuum rather than as a binary. Kinsey developed the scale from models created by his predecessors in human sex research. A primary intention of the scale was to eradicate sexual identity categories altogether in order to eliminate sexual identity-based persecutions and to promote equal rights. As proponents and opponents of homosexual rights both depended on constructions of sexual identity to advance their agendas, Kinsey's ideal was never realized. The scale nonetheless continues to challenge postmodern associations of identity and sexuality.
On the Movement of the Ribosome Along the Messenger Ribonucleic Acid and on Apparent Changes in Ribosome Conformation During Protein Synthesis

During the translation of mRNA into polypeptide, the ribosome moves along the mRNA in the 5′ to 3′ direction (1). Each aminoacyl residue in the polypeptide is specified by three adjacent nucleotides (codon) in mRNA (2). Consequently, it is expected that the ribosome should move the length of three nucleotides when adding one aminoacyl residue to the growing polypeptide. In this communication, we present experiments bearing out this expectation.
Capacity of electromagnetic communication modes in a noise-limited optical system

We present capacity bounds of an optical system that communicates using electromagnetic waves between a transmitter and a receiver. The bounds are investigated in conjunction with a rigorous theory of degrees of freedom (DOF) in the presence of noise. By taking into account the different signal-to-noise ratio (SNR) levels, an optimal number of DOF that provides the maximum capacity is defined. We find that for moderate noise levels, the DOF estimate of the number of active modes is approximately equal to the optimum number of channels obtained by a more rigorous water-filling procedure. On the other hand, for very low- or high-SNR regions, the maximum capacity can be obtained using less or more channels compared to the number of communicating modes given by the DOF theory. In general, the capacity is shown to increase with increasing size of the transmitting and receiving volumes, whereas it decreases with an increase in the separation between volumes. Under the practical channel constraints of noise and finite available power, the capacity upper bound can be estimated by the well-known iterative water-filling solution to determine the optimal power allocation into the subchannels corresponding to the set of singular values when channel state information is known at the transmitter.
A Case of Bronchial Foreign Body Removal During Trans-Laryngeal Mask Airway Fiberoptic Bronchoscopy.

Bronchial foreign body is not a rare disease in children and it is urgently necessary to remove this foreign body from the airway to relive life or to prevent further damages and complications. But the innate small size of airways in infants makes it difficult to access by interventional methods such as intubation or bronchoscopy and etc. Laryngeal mask airway is a new way of method of airway management which is relatively recently introduced into medical practice. It gives way to access to airways without reducing the size of airway or incresing airway pressure during procedure through it and have many other advantages compared to the previous traditional endotracheal intubation, especially in infants. We successfully removed a case of bronchial foreign body, peanut, via laryngeal mask airway during fiberoptic bronchoscopy and by this method we can avoid the unnecessary tracheostomy in this 1 year old infant.
Safe use of high intakes of folic acid: research challenges and paths forward

Adequate folic acid intake is an effective dietary-based prevention tool for reducing the risk of neural tube defects. Achieving adequate intake for the prevention of neural tube defects frequently requires the consumption of foods fortified with folic acid and/or the use of folic acid–containing dietary supplements. To date, research on the potential for adverse effects of high intakes of folic acid has been limited. Without such research, it is difficult to define a value for high intake. In May 2015, an expert panel was tasked with examining the available scientific literature and making research recommendations within 4 general categories of potential folate-related adverse health effects: cancer, cognition in conjunction with vitamin B12 deficiency, hypersensitivity-related outcomes, and thyroid and diabetes-related disorders. This article summarizes the expert panel’s conclusions, outlines the challenges faced when reviewing the literature, and examines some of the panel’s recommendations for research.
Tuition in the Public Schools

If financial incentives are to be used to curtail the number of births and to control population numbers, we might consider other options. One possible approach would be a requirement that parents pay at least some portion of the cost of educating their children, a cost now borne by the public at large. The cost is not only substantial; it is increasing rapidly. In 1960 the average expenditure per pupil in public primary and secondary schools was $375; in 1970 it was $816; in 1979 it reached $1,900. The increased cost of education has been outpacing income; public schools have been taking from taxpayers an increasing proportion of their incomes. In 1960 the average expenditure per student constituted 17 percent of per capita personal income; by 1979 it constituted 22 percent.1 Clearly, the public subsidy for education cannot continue to take an expanding share of income; sooner or later, the needs of education will exceed the ability or willingness of the public to provide funds. A decline in educational quality is the likely result. Charging tuition in the public schools might thus not only reduce the birth rate but also simultaneously protect an essential social service.
On the Relation between Local Amenities and House Price Dynamics

This study explores the extent to which local amenities are related to house price volatility, returns and risk-adjusted returns across 238 MSAs. We find strong evidence that high amenity areas experience greater price volatility. In regards to returns, high amenity areas experience greater (lower) real returns in appreciating (depreciating) markets. However, high amenity areas experience little to no abnormal risk-adjusted returns. Results from the study are robust to an endogenous treatment of amenities and land supply elasticity. Overall, we conclude that the desirability of a metropolitan area is a significant channel through which land values drive house price dynamics.
Optogenetic Immunomodulation: Shedding Light on Antitumor Immunity

Microbial opsin-based optogenetic tools have been transformative for neuroscience. To extend optogenetic approaches to the immune system to remotely control immune responses with superior spatiotemporal precision, pioneering tools have recently been crafted to modulate lymphocyte trafficking, inflammasome activation, dendritic cell (DC) maturation, and antitumor immunity through the photoactivation of engineered chemokine receptors and calcium release-activated calcium channels. We highlight herein some conceptual design strategies for installing light sensitivities into the immune signaling network and, in parallel, we propose potential solutions for in vivo optogenetic applications in living organisms with near-infrared light-responsive upconversion nanomaterials. Moreover, to move beyond proof-of-concept into translational applications, we discuss future prospects for integrating personalized immunoengineering with optogenetics to overcome critical hurdles in cancer immunotherapy.
Calcium and phosphorus requirement of swine from weaning to market weight: I. Development of response curves for performance.

Three trials using 300 pigs were conducted to establish response surfaces for effects of calcium and phosphorus (Ca/P) levels and of time on postweaning pig performance. Five dietary Ca/P levels (70, 85, 100, 115 and 130% of the NRC [1979] estimated dietary Ca and P requirements) were fed from weaning to market weight. Twelve replicates, each consisting of five pigs, were used across the three trials, and one pig per replicate was slaughtered every 4 wk following the start of the trials. Efficiency of feed utilization (G:F) was insensitive to diet within the range of Ca/P levels used, whereas ADG and average daily feed intake (ADFI) were linearly (P less than .01) and quadratically (p less than .01) related to both diet and weigh period. Asymptotic models relating continuous effects of total Ca + P intake (average grams per day of Ca + P) relative to the NRC estimated Ca + P intake and days on test at the midpoint of each weigh period were fitted to the data and used to derive response surfaces for ADG and ADFI. Ninety, ninety-five and ninety-eight percent of maximum ADG, ADFI and G:F also were determined; 98% of maximum ADG was reached with a Ca and P intake of 99.8% of NRC Ca/P estimates, whereas Ca and P intakes of 95.3 and 83.5% of NRC estimates were required to produce 98% of maximum ADFI and G:F, respectively.
Emotions in Luxury Consumption: An Exploratory Comparison Between Two Cultures—An Extended Abstract

Luxury items are objects of desire that provide pleasure and satisfy psychological and functional needs (Dubois and Duquesne 1993). As such, emotion, both positive (e.g., pleasure) and negative (e.g., guilt associated with overspending), may play a critical role in luxury consumption. However, much of past literature have focused on categories of luxury brands, types of luxury consumers, and their motivation or attitude; limited research have explored emotions in luxury consumption specifically. Only limited aspects of emotion such as pride (McFerran and 2014) and guilt among young female Taiwanese consumers (Wu et al. 2015) have been explored. In addition, while differences on motivations of luxury consumption have been found between Asian and Western societies (Wang and Waller 2006; Wong and Ahuvia 1998), little is known regarding emotional differences associated with luxury consumption, if any (Vigneron and Johnson 2004). Thus, understanding emotion from a cross-cultural perspective will help marketers build relevant marketing and promotional strategies for the luxury market.
Verbal inflection in Kwawu Akan

Morphological processes in Kwawu are argued to be governed by a condition which states that words are morphologically analyzable only in terms of properties of the head of the word. The head of an affi~ed word is the most external affix. Certain rules apply only to bare stems and not to words with affixes. A verb formed by reanalyzing adjacent verbs as a single morphological word is accessible to these rules if its head is a stem; non-head roots in the reanalyzed verb are inaccessible to all morphological rules, as predicted.
Derrida and messianic subjectivity: a hauntology of revealability

In Specters of Marx, Jacques Derrida argues that the category of hauntology should replace the canonical understanding of ontology. By invoking the trope of the ghost, hauntology helps to demonstra...
Tunicamycin Exposure Triggers Apopotosis by Superoxide Formation from Site IIIQo of Mitochondrial Complex III

Tunicamycin is a model inducer of endoplasmic reticulum stress and cell death. Its primary effect is inhibition of N-linked protein glycosylation, which leads to accumulation of misfolded proteins and the endoplasmic reticulum unfolded protein response. This then leads to alteration of mitochondrial function and ultimately to caspase activation and cell death. Recently, we reported the identification of small molecules that prevent superoxide formation at site IIIQo of mitochondrial Complex III without impairing oxidative phosphorylation (S3QELs, suppressors of site IIIQo electron leak), and that S3QELs decreased tunicamycin-induced caspase activation in INS-1 insulinoma cells (Orr et al. (2015) Nature Chem Biol 11, 834-836). Here we aimed to find whether this phenomenon also occurs in murine C2C12 myoblasts. C2C12 myoblasts, which are commonly used for analysis of bioenergetics and metabolism were exposed to 1 µM tunicamycin for 24 h with or without different chemical classes of S3QELs. Cells were then stained for activated caspases 3 and 7 (CellEvent), cell death (propidium iodide) and nuclei (Hoechst 33342). Exposure to tunicamycin led to apoptotic cell death in 10% and necrotic cell death in 5% of cells. Addition of 10 µM S3QEL2 or S3QEL3 decreased apoptosis by 30% (p
Statistical cut response of high-performance single fibers

Single high-performance fibers (Kevlar® K129, Twaron® 2040, Technora® T200, Dyneema® SK76, Zylon® AS, Vectran® HT, and S-glass) are subject to lateral cutting action by an industrial blade. Due to ...
An Examination of the Evidence-Base of School-Wide Positive Behavior Interventions and Supports Through Two Quality Appraisal Processes:

Thousands of schools across the United States, and worldwide, implement School-Wide Positive Behavioral Interventions and Supports (SWPBIS). SWPBIS provides a framework whereby teams of educators e...
An Umbrian inscription at Poggio Civitate (Murlo)

The Etruscan site of Poggio Civitate has preserved a small corpus of inscriptions dating to the 7th century BCE phase of the site. Among them is one outlier: a fragmentary text inscribed on the rim of a utilitarian vessel manufactured at the site. The text and alphabet appear Umbrian rather than Etruscan. The find spot and date of the fragment are discussed, possible interpretations of the text are offered, and attempt is made to situate the inscription within its social context.
Management of Necrotizing Pancreatitis by Planned, Repeated Necrosectomy/Débridement with Delayed Primary Closure

The introduction of formal widespread pancreatic and peripancreatic necrosectomy, as opposed to simple peripancreatic drainage, has markedly decreased the mortality of necrotizing pancreatitis. Nevertheless, operative mortality remains about 20%. Several different techniques have been described to manage the peripancreatic space after necrosectomy to allow continued drainage and debridement. These techniques include widespread closed/open tube drainage [17], open controlled packing or so-called “marsupialization” [2–4, 11, 15], closed continuous lavage [1, 8, 16] and repeated, planned reoperative debridement [14]. This chapter discusses our technique of repeated, planned reoperative debridement following the initial operative necrosectomy. We believe that this approach maximizes debridement of pancreatic and peripancreatic necrotic tissue and thereby minimizes the incidence of recurrent intra-abdominal sepsis.
Immunolocalization of TGF-beta 1, TGF-beta 2, and TGF-beta 3 in the anterior segment of the human eye.

Purpose To determine the distribution of transforming growth factor type beta (TGF-beta) in the anterior segment of the human eye. This knowledge is important because TGF-beta may regulate various physiologic responses in the anterior segment by controlling cell proliferation and differentiation, angiogenesis, and extracellular matrix composition. Methods Immunohistochemical methods were used to localize the beta 1, beta 2, and beta 3 isoforms of TGF-beta in the anterior segment of the human eye. Results Eight of eight eyes (six eye bank specimens and two eyes enucleated because of choroidal melanoma) exhibited staining for at least one of the TGF-beta isoforms. TGF-beta 1 was found in superficial limbal epithelial cells (four of eight eyes) and in the stroma proximal to the ciliary processes (seven of eight eyes). TGF-beta 2 was found in superficial limbal epithelial cells (six of eight eyes), the conjunctival stroma (eight of eight eyes), in the ciliary processes (three of eight eyes), and in a diffuse distribution in the region of the radial and circular muscles of the ciliary body (eight of eight eyes). In addition, TGF-beta 2 was found in the stroma adjacent to the pigmented epithelium in the pars plana (eight of eight eyes). TGF-beta 3 was found in white blood cells in one of eight specimens; otherwise it was not found in the anterior segment. The corneal stroma, corneal endothelium, trabecular meshwork, iris, and ciliary epithelia did not exhibit immunoreactivity with the antibodies used in this study. Conclusion TGF-beta 1 and TGF-beta 2 have a distinct and specific distribution in the anterior segment of the adult human eye.
Restoration of spermatogenesis after exposure to toxicants: genetic implications.

Many men have been sterilized by exposure to radiation and chemotherapy agents as treatment for cancer; radiation and almost all of the chemotherapeutics are also mutagens. In the United States alone, 17,000 men 15 to 45 years old are diagnosed each year with Hodgkin’s disease, lymphoma, bone and soft tissue sarcomas, testicular cancer, or leukemia (Landis et al., 1999). Of these, over 2,400 are long-term survivors that were treated with doses of alkylating agents, platinum drugs, or radiation sufficient to induce prolonged azoospermia. In addition, 6,000 boys under 15 are diagnosed each year with cancer, including leukemia, nervous system tumors, lymphomas, and other solid tumors. About 80% of them receive chemotherapy or gonadal irradiation, and about 550 of the long-term survivors are azoospermic when they reach adulthood.
Peer Coaching and Motivational Interviewing in Postsecondary Settings: Connecting Retention Theory with Practice

Academic coaching is growing as a form of retention support, but questions surrounding what coaching should be continue to limit its potential. We argue that a resolution lies in increasing alignme...
Strengthening Strategic Planning Through Diverse Collaborations

Abstract In previous strategic plan development, the University of Maryland, Baltimore (UMB) Health Sciences and Human Services Library (HS/HSL) used a “library knows best” approach, where the Library Leadership Team (the Team) decided on the focus, time frame, and format of the plan. Breaking with this tradition, the Team embarked on a new strategic planning mission to deliberately and inclusively reach out to users. This effort resulted in the first strategic plan constructed collaboratively with stakeholder input acquired by exhaustive outreach efforts. The Team developed a new collaborative methodology for collecting user input and documented the process throughout. The Team knew the strengths, weaknesses, and capabilities of the environment. It was important to understand users and build a strategic plan focused on their success. This chapter reports on the collaborative and inclusive planning process key to the HS/HSL's strategic planning success.
"In a Perfect World, You Wouldn't Have to Work the System to Get the Things You Need to Survive": A Pilot Study About Trans Health Care Possibilities.

Abstract Purpose: aTHeNA (a Trans Health Needs Assessment) is a pilot study exploring the perspectives and experiences of trans people in western Massachusetts on and with health care. This study e...
The finite temperature transition for 3-flavour lattice QCD at finite isospin density

We simulate 3-flavour lattice QCD with a small chemical potential μ I for isospin, at temperatures close to the finite temperature transition. Using quark masses just above the critical mass for zero chemical potential, we determine the position of the transition from hadronic matter to a quark-gluon plasma as a function of μ I . We see evidence for a critical endpoint where the transition changes from a crossover to a first-order transition as μ I is increased. We argue that QCD at finite μ I and QCD at finite quark-number chemical potential μ should behave similarly in this region.
Protease Inhibitors, Saquinavir and Darunavir, Inhibit Oligodendrocyte Maturation: Implications for Lysosomal Stress

Despite the introduction of antiretroviral (ARV) therapy (ART), approximately 30-50% of people living with human immunodeficiency virus-1 (HIV-1) will develop a spectrum of measurable neurocognitive dysfunction, collectively called HIV-associated neurocognitive disorder (HAND). While the clinical manifestations of HAND have changed with the advent of ART, certain pathological features have endured, including white matter alterations and dysfunction. The persistence of white matter alterations in the post-ART era suggests that ARV drugs themselves may contribute to HAND pathology. Our group has previously demonstrated that two ARV compounds from the protease inhibitor (PI) class, ritonavir and lopinavir, inhibit oligodendrocyte maturation and myelin protein production. We hypothesized that other members of the PI class, saquinavir and darunavir, could also negatively impact oligodendrocyte differentiation. Here we demonstrate that treating primary rat oligodendrocyte precursor cells with therapeutically relevant concentrations of either ARV drug results in a concentration-dependent inhibition of oligodendrocyte maturation in vitro. Furthermore, we show that acidifying endolysosomal pH via a mucolipin transient receptor potential channel 1 (TRPML1) agonist provides protection against saquinavir- and darunavir-induced inhibition of oligodendrocyte maturation. Moreover, our findings suggest, for the first time, an imperative role of proper endolysosomal pH in regulating OL differentation, and that therapeutic targeting of endolysosomes may provide protection against ARV-induced oligodendrocyte dysregulation. Graphical Abstract Treatment of primary rat oligodendrocyte precursor cells with therapeutically relevant concentrations of either antiretroviral compound of the protease inhibitor class, darunavir or saquinavir, results in a concentration-dependent inhibition of oligodendrocyte maturation in vitro. Additionally, in darunavir or saquinavir-treated cultures we observed a concentration-dependent decrease in the number of acidic lysosomes, via immunostaining with LysoTracker Red, compared with vehicle-treated cultures. Finally, we showed that acidifying endolysosomal pH via a mucolipin transient receptor potential channel 1 (TRPML1) agonist provides protection against saquinavir- or darunavir-induced inhibition of oligodendrocyte maturation. Our findings suggest, for the first time, a critical role of proper endolysosomal pH in regulating OL differentation, and that therapeutic targeting of endolysosomes may provide protection against antiretroviral-induced oligodendrocyte dysregulation.
Exploiting uncertain timing information in time-based SAR ADCs

Time-based successive approximation register (SAR) analogue-to-digital converters (ADCs) are gaining attraction in ultra-low voltage circuit design. Such ADCs typically use multi-stage voltage controlled delay lines (VCDLs) to perform voltage to time conversion in order to mitigate limited headroom of voltage signals. Although multi-stage VCDLs are used, only the outputs of the final VCDL stages are compared during bit trials. This work demonstrates that additional bit information can be extracted by scavenging timing information revealed at VCDL intermediate stages. The additional bit information can be used to accelerate the ADC conversion process or improve signal-to-noise distortion ratio (SNDR). To cope with uncertainties associated with signals from VCDL intermediate stages, an uncertainty-tolerant SAR procedure is developed. Also, this work presents techniques for adaptively selecting which intermediate stage signals to be tapped along the conversion process. The proposed techniques are applied in the design of a 0.4 V 9-bit SAR ADC in a 130 nm CMOS technology. Silicon measurement results show that with the additional information extracted from VCDL intermediate stages the conversion for the vast majority of ADC inputs can be completed in 7 or 8 clock cycles. Measurement results also demonstrate the potentials of using the intermediate stage signals to improve ADC SNDR.
Autonomic/Central Coupling Boosts Working Memory in Healthy Young Adults

Working memory (WM) is an executive function that can improve with training. However, the precise mechanism for this improvement is not known. Studies have shown greater WM gains after a period of sleep than a similar period of wake (Kuriyama et al. 2008a; Zinke, Noack, and Born 2018), with WM improvement correlated with slow wave activity (SWA; 0.5-1Hz) during slow wave sleep (SWS) (Sattari et al. 2019; Pugin et al. 2015; Ferrarelli et al. 2019). A different body of literature has suggested an important role for autonomic activity during wake for WM (Hansen et al. 2004; Mosley, Laborde, and Kavanagh 2018). A recent study from our group reported that the temporal coupling of autonomic and central events (ACEs) during sleep was associated with memory consolidation (Naji et al. 2019). We found that heart rate bursts (HR bursts) during non-rapid eye movement (NREM) sleep are accompanied by increases in SWA and sigma (12-15Hz) power, as well as increases in the high-frequency (HF) component of the RR interval, reflecting vagal rebound. In addition, ACEs predict long-term, episodic memory improvement. Building on these previous results, we examined whether ACEs may also contribute to gains in WM. We tested 104 young adults in an operation span task (OSPAN) in the morning and evening, with either a nap (with electroencephalography (EEG) and electrocardiography (ECG)) or wake between testing sessions. We identified HR bursts in the ECG and replicated the increases in SWA and sigma prior to peak of the HR burst, as well as vagal rebound after the peak. Furthermore, we showed sleep-dependent WM improvement, which was predicted by ACE activity. Using regression analyses, we discovered that significantly more variance in WM improvement could be explained with ACE variables than with overall sleep activity not time-locked with ECG. These results provide the first evidence that coordinated autonomic and central events play a significant role in sleep-related WM improvement and implicate the potential of autonomic interventions during sleep for cognitive enhancement.
A comparison of perioperative safety for breast augmentation in cis- vs. trans patients.

Background Gender-affirming surgery provides a psychosocial benefit to transgender women. However, increased medical complexity within the transgender population has limited access for some transgender women. This study compared patient population comorbidities and 30-day peri-operative safety following primary augmentation mammoplasty between cis- and transgender women. Methods Data were extracted from the National Surgical Quality Improvement Program (NSQIP) database between 2007 and 2016. Transgender patients were identified using ICD-9 &10 codes for gender dysphoria. Categorical variables were compared using chi-squared and Fisher's exact tests while independent t-tests were used for continuous variables. Statistical significance was set at P<0.05. Results There were 4,234 breast augmentations identified in cisgender women and 137 in transgender women. Transgender women had a higher frequency of ASA-II and ASA-III patients (P<0.001), diabetes (P<0.001), hypertension (P=0.006), and active smoking status (P<0.001). Despite the higher comorbidity burden and routine use of hormonal therapy, there were no significant differences between populations in major or minor peri-operative complication rates. Conclusions Top surgery improves quality of life in transgender women. Despite the more complex pre-operative risk profile in the transgender population, there is no difference in peri-operative safety profiles. Plastic surgeons treating this patient population should consider more liberal surgical indications for reconstructive top surgery compared with cosmetic breast augmentation.
Ethnic and biological differences in the association between physical activity and survival after breast cancer

Physical activity is recommended for most cancer patients as a nonpharmacological therapy to improve prognosis. Few studies have investigated the association between physical activity and breast cancer prognosis by ethnicity, biological, and modifiable risk factors for mortality. We investigated the association between physical activity and long-term survival among breast cancer survivors. A total of 397 survivors (96 Hispanic and 301 non-Hispanic White (NHW)) from the New Mexico HEAL study contributed baseline and biological data approximately 6 months after diagnosis. Study outcomes included all-cause, breast cancer-specific, and non-breast cancer mortality. The exposure was self-reported physical activity within the past month. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox Proportional Hazards regression. A total of 133 deaths (53 breast cancer-specific deaths) were observed after a median follow-up time of 13 years. Engaging in >6.9 metabolic equivalent hours/week (MET-h/week) of moderate to vigorous physical activity (active) was inversely associated with all-cause mortality among all women (HR 0.66, 95% CI 0.43-0.99) and NHWs (HR 0.58, 95% CI 0.36-0.94). Active NHW women also had a reduced risk of non-breast cancer mortality (HR 0.56, 95% CI 0.31-0.99), compared to inactive women (0 MET-h/week). In subgroups, we observed the inverse associations with all-cause mortality among women >58 years old (p-interaction= 0.03) and with localized stage (p-interaction = 0.046). Our results confirm the protective association between physical activity and mortality after breast cancer diagnosis, and demonstrate that this association significantly differs by age and cancer stage. Larger studies are warranted to substantiate our findings.
Reduction of Glut1 in the neural retina but not the RPE alleviates polyol accumulation and normalizes early characteristics of diabetic retinopathy

Hyperglycemia is a key determinant for development of diabetic retinopathy (DR). Inadequate glycemic control exacerbates retinopathy, while normalization of glucose levels delays its progression. In hyperglycemia, hexokinase is saturated and excess glucose is metabolized to sorbitol by aldose reductase via the polyol pathway. Therapies to reduce retinal polyol accumulation for the prevention of DR have been elusive because of low sorbitol dehydrogenase levels in the retina and inadequate inhibition of aldose reductase. Using systemic and conditional genetic inactivation, we targeted the primary facilitative glucose transporter in the retina, Glut1, as a preventative therapeutic in diabetic male and female mice. Unlike WT diabetics, diabetic Glut1+/− mice did not display elevated Glut1 levels in the retina. Furthermore, diabetic Glut1+/− mice exhibited ameliorated ERG defects, inflammation, and oxidative stress, which was correlated with a significant reduction in retinal sorbitol accumulation. Retinal pigment epithelium-specific reduction of Glut1 did not prevent an increase in retinal sorbitol content or early hallmarks of DR. However, like diabetic Glut1+/− mice, reduction of Glut1 specifically in the retina mitigated polyol accumulation and diminished retinal dysfunction and the elevation of markers for oxidative stress and inflammation associated with diabetes. These results suggest that modulation of retinal polyol accumulation via Glut1 in photoreceptors can circumvent the difficulties in regulating systemic glucose metabolism and be exploited to prevent DR. SIGNIFICANCE STATEMENT Diabetic retinopathy affects one-third of diabetic patients and is the primary cause of vision loss in adults 20-74 years of age. While anti-VEGF and photocoagulation treatments for the late-stage vision threatening complications can prevent vision loss, a significant proportion of patients do not respond to anti-VEGF therapies, and mechanisms to stop progression of early-stage symptoms remain elusive. Glut1 is the primary facilitative glucose transporter for the retina. We determined that a moderate reduction in Glut1 levels, specifically in the retina, but not the retinal pigment epithelium, was sufficient to prevent retinal polyol accumulation and the earliest functional defects to be identified in the diabetic retina. Our study defines modulation of Glut1 in retinal neurons as a targetable molecule for prevention of diabetic retinopathy.
Design Rules, Volume 2: Chapter 5—Ecosystems and Complementarities

The purpose of this chapter is to introduce two new building blocks to the theory of how technology shapes organizations. The first is a new layer of organization structure: a business “ecosystem.” The second is the economic concept of “complementarity.” Ecosystems are groups of autonomous firms and individuals whose actions and investments create joint value. Ecosystems are defined by economic complementarities among their members: the value they create acting together is greater than the value they can create acting separately. The modern theory of complementarity thus helps to explain when and why ecosystems survive in the greater economy. In the first half of this chapter, I define business ecosystems and show how they are related to task networks, transactions, transaction free zones, and corporations. I then describe the methods by which ecosystems are coordinated. The second half of the chapter investigates how economic complementarities influence ecosystems. Within ecosystems, centripetal forces “pull” firms together giving them incentives to combine. Conversely, centrifugal forces “push” firms apart providing incentives to remain separate. The continued existence of an ecosystem requires a balance of these forces, so that the system neither collapses into several large firms nor dissipates into a group of unrelated firms. In the final sections of the chapter, I identify necessary mathematical conditions for an ecosystem to survive as a dynamic equilibrium in the larger economy.
Dual-eligible beneficiaries and inadequate access to primary care providers

OBJECTIVES: To determine whether enough primary care providers are in close proximity to where dual-eligible beneficiaries live to provide the capacity needed for integrated care models. STUDY DESIGN: Secondary data analysis using dual-eligible enrollment data and health care workforce data. METHODS: We determined the density of dual-eligible beneficiaries per 1000 population in 2017 for each of 3142 US counties. County-level supply of primary care physicians (PCPs), primary care nurse practitioners, and physician assistants was determined. RESULTS: One-third of the 791 counties with the highest density of dual-eligible beneficiaries had PCP shortages. Counties with the highest density of dual-eligible beneficiaries and the fewest primary care clinicians of any type were concentrated in Southeastern states. These areas also had some of the highest coronavirus disease 2019 outbreaks within their states. CONCLUSIONS: States in the Southeastern region of the United States with some of the most restrictive scope-of-practice laws have an inadequate supply of primary care providers to serve a high concentration of dual-eligible beneficiaries. The fragmented care of the dually eligible population leads to extremely high costs, prompting policy makers to consider integrated delivery models that emphasize primary care. However, primary care workforce shortages will be an enduring challenge without scope-of-practice reforms.
Students’ psychophysiological reactivity to trigger warnings

Trigger warnings are defined as alerts presented before media to warn that the content may represent a trauma reminder. Their usefulness in higher education has been at the center of debate. While originally created to help individuals with posttraumatic stress symptoms decide whether or not to engage with material that could elicit, or “trigger” symptoms, trigger warnings have been implicated in perpetuating the avoidant behaviors that maintain the posttraumatic stress syndrome. Much of the literature thus far describes trigger warnings as creating a nocebo effect (fostering negative expectations), but these studies use only self-report measures. The present study aimed to build upon the nocebo hypothesis to assess psychophysiological responses (heart rate, respiration rate, skin conductance) to the phrase “trigger warning” as compared to alternative warning phrases and to examine whether PTSD symptoms or receptivity of trigger warnings influence this reactivity. Students (N = 106) were randomly assigned to see either the phrase “trigger warning” a PG-13 movie rating, or no warning before watching a movie clip. Viewing the trigger warning increased heart rate, respiration rate, and skin conductance measures more than viewing either the PG-13 or control stimuli. Moreover, posttraumatic stress symptoms and receptivity towards trigger warnings did not account for the relationship between warning exposure and reactivity. Ideas for future research and future trigger warning deployment are discussed.