cssi/SciSciGPT-SciSciNet huggingface dataset:
Discovery pharmacokinetic studies in mice using serial microsampling, dried blood spots and microbore LC-MS/MS

Background: Initial pharmacokinetic (PK) studies of discovery compounds are conducted in mice to demonstrate exposure prior to conducting efficacy studies. PK information obtained from a single mouse by serial blood microsampling, dried blood spot collection and analyses using microbore (1 mm internal diameter column) LC–MS/MS is presented. Ex vivo blood to plasma concentration ratios (BPRs) from mouse PK studies were compared with in vitro BPRs for 15 compounds. Results: Two compounds were orally dosed and blood was collected at time points via serial blood sampling. The calculated PK parameters (AUC, Tmax and Cmax) were comparable across liquid blood, dried blood spot and plasma matrices. The BPR results from both methods were comparable. Conclusion: Serial blood microsampling has led to reduced animal and compound usage with improved PK data. Ex vivo BPR is suitable in a discovery setting. Microbore LC–MS/MS is well suited in instances where sample volume is limited, and enables faster analyses, reduce...
Clinical characteristics of psychiatrically referred adolescent outpatients with substance use disorder.

ABSTRACT Objective There is increasing interest in the developmental relationship of psychopathology and substance use disorders (SUD) in youths. Because the bulk of literature is focused in inpatient or incarcerated youths, inferences and generalizations are limited in outpatient settings. The clinical characteristics of psychiatrically referred outpatients were studied to determine whether differences existed in the nature and severity of comorbid psychiatric disorders when substance abuse was involved. Method All diagnoses were derived from structured psychiatric interviews completed on all youths on intake assessment. Adolescents with an identified SUD ( n = 38) were compared with those without SUD ( n = 321) on a number of variables including past and current psychopathology, cognitive and school functioning, and overall impairment. Results Eleven percent of referred outpatients (mean age = 15.9 ± 1.3 years) met full criteria for a SUD by parental report. Controlling for age, adolescents with SUD had higher risk for mood and disruptive behavioral disorders compared with psychiatric controls. In the majority of cases, the onset of psychopathology preceded the onset of SUD by at least 1 year. The group with SUD also had lower overall functioning and more school dysfunction and psychiatric hospitalizations than their non-SUD peers. Conclusions Despite the small number of adolescents with SUD in this sample, these data indicate that SUD is common in outpatient psychiatry referrals. Youths with SUD appear to be at increased risk for more psychopathology and dysfunction in a number of domains. J. Am. Acad. Child Adolesc. Psychiatry, 1997, 36(7):941–947.
On the complexity of approximating the VC dimension

We study the complexity of approximating the VC dimension of a collection of sets, when the sets are encoded succinctly by a small circuit. We show that this problem is: /spl Sigma//sub 3//sup p/-hard to approximate to within a factor 2-/spl epsiv/ for any /spl epsiv/>0; approximable in A/spl Mscr/ to within a factor 2; and A/spl Mscr/-hard to approximate to within a factor N/sup /spl epsiv// for some constant /spl epsiv/>0. To obtain the /spl Sigma//sub 3//sup 9/-hardness results we solve a randomness extraction problem using list-decodable binary codes; for the positive results we utilize the Sauer-Shelah(-Perles) Lemma. The exact value of /spl epsiv/ in the A/spl Mscr/-hardness result depends on the degree achievable by explicit disperser constructions.
All obese individuals are not created equal: insulin resistance is the major determinant of cardiovascular disease in overweight/obese individuals.

The ability of insulin to mediate glucose disposal varies more than six-fold in an apparently healthy population, and approximately one third of the most insulin-resistant of these individuals are at increased risk to develop cardiovascular disease. Differences in degree of adiposity account for approximately 25% of this variability, and another 25% varies as a function of level of physical fitness. The more overweight/obese the person, the more likely they are to be insulin-resistant and at increased risk of cardiovascular disease, but substantial numbers of overweight/obese individuals remain insulin-sensitive, and not all insulinresistant persons are obese. Of greater clinical relevance is evidence that the metabolic benefit and decrease in risk of cardiovascular disease following weight loss occurs primarily in those overweight/obese individuals that are also insulin resistant. The relationship between insulin resistance and overall obesity, as assessed by measurement of body mass index, is essentially the same as the relationship between insulin action and abdominal obesity as quantified by determining waist circumference. Finally, there appears to be a comparable relationship between insulin-mediated glucose disposal and amount of visceral fat, subcutaneous fat, and total fat as quantified by various imaging techniques, and the magnitude of these relationships is no greater than that between insulin action and simple measure of body mass index. Diabetes Vasc Dis Res 2005;2:105‐12
Evaluation of Four Herbicides and Tillage for Weed Control on 1-0 Planted Tree Seedlings

Azafenidin, sulfometuron, pendimethalin, and simazine were applied alone and in combination to 1-0 seedlings of nine hardwood and one conifer species. Percent bare ground at 30, 60, and 90 days, diameter and height growth of the seedlings were determined for 16 herbicide treatments, tillage and a control. Azafenidin applications alone and in combination with sulfometuron resulted in about 85% bare ground 90 days post-treatment. There were significant differences for diameter, height growth, and volume among the treatments for every species. No single treatment ranked best for all species, but comparison of the mean ranks of the treatments for all species indicated that azafenidin and pendimethalin resulted in the most growth. Azafenidin-treated seedlings also had the greatest volume at the end of the season.
Development of an Enzyme-linked Immunosorbent Assay to Detect Chicken Parvovirus-specific Antibodies

Here we report the development and application of an enzyme-linked immunosorbent assay (ELISA) to detect parvovirus-specific antibodies in chicken sera. We used an approach previously described for other parvoviruses to clone and express viral structural proteins in insect cells from recombinant baculovirus vectors. In baculovirus recombinant-infected Sf9 cells, the chicken parvovirus (ChPV) structural viral protein 2 (VP2) was detected as an abundant protein, and the 60-kDa VP2 strongly reacted with parvovirus-infected chicken serum in Western blot. A semipurified VP2 was then used in capture ELISA. Sera from chickens experimentally infected with ChPV and sera from uninfected chickens were tested to evaluate the assay. The ELISA was 93.3% sensitive and 100% specific in detecting ChPV-infected birds. Subsequent assays identified IgG type ChPV-specific maternally acquired antibodies in day-old chickens and demonstrated the production of virus-specific antibodies in young birds following infection with ChPV. In our study, a specific antibody response of infected chickens was observed starting with IgM production between 14 and 21 days postinfection (DPI) and switching into a predominant IgG response by 32 DPI. The availability of an ELISA for detection of virus-specific antibodies and its ability to differentiate between maternally acquired antibodies and antibodies produced following acute infection could prove to be a valuable tool to characterize pathobiological properties and immunogenicity of ChPV.
What is Supergravity and which of its Goals have been Reached

It is a relief to show you the beautiful vistas of supergravity now that we have been engulfed here on top of this mountain in fog and rain for more than a week. Local Fermi-Bose symmetry (= local supersymmetry) can only be implemented in curved spacetime. Thus supergravity is born by joining particle physics and relativity. To promote contact and further offspring this school was organized.
Perspective: Title VI, Healthcare Reform, and the Need for a State Antidiscrimination Law

“It might be that civil rights laws often go unenforced; it might be that current inequities spring from past prejudice and long standing economic differences that are not entirely reachable by law; or it might be that the law sometimes fails to reflect, and consequently fails to correct, the barriers faced by people of color.” – Derrick Bell1 Equal access to quality health care is a crucial issue that the United States (US) is facing. For too long, we have denied too many Americans equal access to quality health care based on race, ethnicity, and gender. Many factors contribute to disparities: cultural incompetence of health care providers, socioeconomic inequities, disparate impact of racially neutral practices and policies, inadequacy of civil rights laws and enforcement, and multiple forms of discrimination. These ­disparities exist in health status, access to health care services, participation in health research, and receipt of health care financing. This disparity in health care is doubly significant given the devastating racial disparity in health status that exists. The combination of racial disparity in health status, institutional racism in health care, inadequate legal protection, and the failure of health care reform to adequately address racial discrimination in health care points to a need for a major civil rights law for health care. Several federal laws address access to health care: Title XVIII (Medicare), Title XIX (Medicaid) of the Social Security Act, Title IX, and the Hill Burton Act. The only federal laws related to eliminating racial discrimination in health care delivery are Title VI of the Civil Rights Act and § 1557 of the Patient Protection and Affordable Care Act (hereinafter, “Affordable Care Act.” Racial inequality in health care persists in the United States despite laws against racial discrimination, in significant part because of the inadequacy of Title VI, and the Affordable Care Act has done little to correct the problem.
Ultrathin and Flexible Single Crystal Silicon Mini-Modules

There is a high interest for having power on demand through ultra-light, highly-efficient, and flexible photovoltaic systems. Currently, the most efficient technologies are based on a rigid format using single crystal materials and the flexible ones are based on not so efficient polycrystalline or amorphous materials. We present a new method to produce ultrathin and flexible solar cells made of single crystal crystalline silicon. We propose the use of ultrathin (<20 μm) segmented silicon (less than 1 mm in diameter) created with microsystems tools and techniques. The processing of the cells, including passivation and metallization, was done on standard thickness wafers with standard tools. The cell design is a back, point contact, interdigitated cell. The finished cells were transferred onto a 100 μm thick flexible glass substrate with patterned metal traces. Interconnections between the cell and substrate were formed with a solder reflow step. The first demonstration module prototypes transferred and connected 474 micro cells all at once. The conversion efficiency of the mini module was 12.4% with a total Voc = 7.8V. The principle shown here can be used to transfer the cells onto other flexible substrates (i.e. polymers) and achieve an ultra-light, highly efficient, and flexible photovoltaic system.
Site Response Analysis of Liquefying Sites

Two case histories of liquefaction at down-hole array stations were analyzed using one-dimensional dynamic site response procedures with three different constitutive models for liquefiable soils. The two sites were the Port Island Array in the 1995 Kobe Earthquake and the Wildlife Liquefaction Array in the 1987 Superstition Hills Earthquake. The three constitutive models represent a range of modeling complexity and were run as user-defined models in the finite difference program FLAC. Procedures for calibrating the non-linear constitutive models against field data and the numerical solution procedures are described. Sensitivity of the computed responses to parameter uncertainties was evaluated. The capabilities and limitations of these methods for simulating the observed responses at these sites are discussed.
Superconducting magnesium diboride coatings for radio frequency cavities fabricated by hybrid physical-chemical vapor deposition

We have investigated the coating of an inner surface of superconducting radio frequency cavities with a magnesium diboride thin film by hybrid physical-chemical vapor deposition (HPCVD). To simulate a 6 GHz rf cavity, a straight stainless steel tube of 1.5-inch inner diameter and a dummy stainless steel cavity were employed, on which small sapphire and metal substrates were mounted at different locations. The ${\mathrm{MgB}}_{2}$ films on these substrates showed uniformly good superconducting properties including ${T}_{c}$ of 37--40 K, residual resistivity ratio of up to 14, and root-mean-square roughness ${R}_{q}$ of 20--30 nm. This work demonstrates the feasibility of coating the interior of cylindrical and curved objects with ${\mathrm{MgB}}_{2}$ by the HPCVD technique, an important step towards superconducting rf cavities with ${\mathrm{MgB}}_{2}$ coating.
Design of Small-scale Ablative Testing Apparatus with Sample Position and Velocity Control

Ablative materials are extensively used in aerospace applications as a key component of Thermal Protection Systems in both spacecraft and aircrafts. These materials are commonly tested in small-scale testing systems to assess their performance in an economic manner. This study involves the design of an Oxyacetylene Testbed (OTB) based on the one designed by Allcorn et al., with the addition of a linear actuator to correct for material recession that would enable to maintain a constant heat flux, and an infrared pyrometer to measure surface temperature. The system was calibrated using the standard copper slug method, and all samples were tested at 1000 W/cm2. Four different materials were tested using the proposed design: Carbon-carbon, Carbon-phenolic, PyroSic 2704 and PyroSic 4686. All of these samples were equipped with multiple thermocouples placed at different depths in order to calculate the recession rate from the thermocouple times of failure. Thermocouple data were gather by a data-acquisition system, and surface temperature from the IR pyrometer. The recession rates obtained using the proposed system agreed with results previously reported using similar testing systems. The purpose design proved to be a flexible platform upon which future testing capabilities, such an automatic recession correction system, can be added in the future.
Distinguishing characteristics of Mount Graham red squirrel midden sites

The Mount Graham red squirrel (Tamiasciurus hudsonicus grahamensis) was listed as endangered in 1987 because its population was small and declining, its range was restricted, and its remaining habitat was threatened by human activities. We measured vegetational and other physical features around middens of the Mount Graham red squirrel (n = 215) and at random locations (n = 201) in Engelmann spruce (Picea engelmannii)-cork-bark fir (Abies lasiocarpa var. arizona) and transition-zone forests to identify characteristics that distinguish midden sites from random sites. Foliage volume, canopy closure, basal area, tree density 40 cm in diameter at breast height (dbh) were greater (P < 0.005) at midden sites than at random sites in both forest types
In vivo tomographic fluorescence lifetime multiplexing of organ targeted fluorophores

We present theoretical and experimental methods for in vivo fluorescence lifetime multiplexing and validate the approach using implanted and organ targeted fluorophores in mice.
CT Analysis of Congenital Ankylotia with Other Deformity of Children

Objective To explore the diagnostic value of multiplanar reformation of high-resolution computed tomography(HRCT) for congenital ankylotia with other deformity,and improve the recognization of composite otology deformity.Methods The whole clinical,surgical identified data of 82 patients(106 ears) with congenital ankylotia is retrospectively reviewed.61 cases are male and 21 cases are female.The average age is 2.4 years(range from 2 months to 14 years).24 cases are bilateral ankylotia,39 cases are only right ankylotia and 19 cases are only left ankylotia.Most of them are conductive deafness,such as perceptive deafness accompanies inner ear deformity.Results Ankylotia is usually companied complex middle ear deformity,accounting for 72%(76/106),and a low incidence in inner ear deformity is 8%(9/106).Among them,the osseous ankylotia(77 ears) is usually companied the complex middle ear deformity,accounting for 92%(71/77),and inner ear deformity is rare,about 10%(8/77).The incidences of middle ear and the inner ear deformity with membranous atresia(29 ears) are scarce,total accounting for 20%(6/29).Conclusion HRCT multiplanar reformation could be used to observe the anatomical structure of auricle,external auditory canal,middle ear and inner ear in the whole course,has important value in the diagnosis of congenital ankylotia with other deformity.
Predicting critical speeds in various rotordynamics problems

Rotating shafts often experience undesirable large-amplitude whirling oscillations associated with resonance at critical speeds. This paper further develops a nondestructive technique in which measured information about the growing nature of the response is used to predict an incipient critical speed. A number of models of varying degrees of sophistication are developed and tested using the new approach, but the main advantage of the method is that it is model-free and thus possesses considerable practical utility. In addition, further experimental results are presented for the case of two disks mounted on a shaft, and the technique is successfully demonstrated in predicting a critical speed associated with a higher mode.
In the Limelight: Photoreceptors in Cyanobacteria

ABSTRACT Certain cyanobacteria look green if grown in red light and vice versa. This dramatic color change, called complementary chromatic adaptation (CCA), is caused by alterations of the major colored light-harvesting proteins. A major controller of CCA is the cyanobacteriochrome (CBCR) RcaE, a red-green reversible photoreceptor that triggers a complex signal transduction pathway. Now, a new study demonstrates that CCA is also modulated by DpxA, a CBCR that senses yellow and teal (greenish blue) light. DpxA acts to expand the range of wavelengths that can impact CCA, by fine-tuning the process. This dual control of CCA might positively impact the fitness of cells growing in the shade of competing algae or in a water column where light levels and spectral quality change gradually with depth. This discovery adds to the growing number of light-responsive phenomena controlled by multiple CBCRs. Furthermore, the diverse CBCRs which are exclusively found in cyanobacteria have significant biotechnological potential.
The Use of DQ-BSA to Monitor the Turnover of Autophagy-Associated Cargo

There is increasing evidence documenting the critical role played by autophagic and autophagy-associated processes in maintaining cell homeostasis and overall systemic health. Autophagy is considered a degradative as well as a recycling pathway that relies on encapsulated intracellular components trafficking to and fusing with degradative compartments, including lysosomes. In this chapter, we describe the use of DQ™-BSA to study autophagosome–lysosome fusion as well as a means by which to analyze hybrid autophagic pathways. Such noncanonical pathways include LC3-associated phagocytosis, better known as LAP. Both autophagosomes and LAPosomes (LC3-associated phagosomes) deliver cargo for degradation. The use of fluorescent DQ™-BSA in conjugation with autophagic makers and biomarkers of hybrid autophagy offers a reliable technique to monitor the formation of autolysosomes and LAPo-lysosomes in both fixed- and live-cell studies. This technique relies on cleavage of the self-quenched DQ™ Green- or DQ™ Red BSA protease substrates in an acidic compartment to generate a highly fluorescent product.
Validation of a White-light 3D Body Volume Scanner to Assess Body Composition.

Introduction Estimating body fat content has shown to be a better predictor of adiposity-related cardiovascular risk than the commonly used body mass index (BMI). The white-light 3D body volume index (BVI) scanner is a non-invasive device normally used in the clothing industry to assess body shapes and sizes. We assessed the hypothesis that volume obtained by BVI is comparable to the volume obtained by air displacement plethysmography (Bod-Pod) and thus capable of assessing body fat mass using the bi-compartmental principles of body composition. Methods We compared BVI to Bod-pod, a validated bicompartmental method to assess body fat percent that uses pressure/volume relationships in isothermal conditions to estimate body volume. Volume is then used to calculate body density (BD) applying the formula density=Body Mass/Volume. Body fat mass percentage is then calculated using the Siri formula (4.95/BD - 4.50) × 100. Subjects were undergoing a wellness evaluation. Measurements from both devices were obtained the same day. A prediction model for total Bod-pod volume was developed using linear regression based on 80% of the observations (N=971), as follows: Predicted Bod-pod Volume (L)=9.498+0.805*(BVI volume, L)-0.0411*(Age, years)-3.295*(Male=0, Female=1)+0.0554*(BVI volume, L)*(Male=0, Female=1)+0.0282*(Age, years)*(Male=0, Female=1). Predictions for Bod-pod volume based on the estimated model were then calculated for the remaining 20% (N=243) and compared to the volume measured by the Bod-pod. Results Mean age among the 971 individuals was 41.5 ± 12.9 years, 39.4% were men, weight 81.6 ± 20.9 kg, BMI was 27.8 ± 6.3kg/m2. Average difference between volume measured by Bod-pod- predicted volume by BVI was 0.0 L, median: -0.4 L, IQR: -1.8 L to 1.5 L, R2=0.9845. Average difference between body fat measured-predicted was-1%, median: -2.7%, IQR: -13.2 to 9.9, R2=0.9236. Conclusion Volume and BFM can be estimated by using volume measurements obtained by a white- light 3D body scanner and the prediction model developed in this study.
Mechanisms of redox metabolism and cancer cell survival during extracellular matrix detachment

Nontransformed cells that become detached from the extracellular matrix (ECM) undergo dysregulation of redox homeostasis and cell death. In contrast, cancer cells often acquire the ability to mitigate programmed cell death pathways and recalibrate the redox balance to survive after ECM detachment, facilitating metastatic dissemination. Accordingly, recent studies of the mechanisms by which cancer cells overcome ECM detachment–induced metabolic alterations have focused on mechanisms in redox homeostasis. The insights into these mechanisms may inform the development of therapeutics that manipulate redox homeostasis to eliminate ECM-detached cancer cells. Here, we review how ECM-detached cancer cells balance redox metabolism for survival.
Resolving Iron(II) Sorption and Oxidative Growth on Hematite (001) Using Atom Probe Tomography

The distribution of Fe resulting from the autocatalytic interaction of aqueous Fe(II) with the hematite (α-Fe2O3) (001) surface was directly mapped in three dimensions (3D) for the first time, using Fe isotopic labeling and atom probe tomography (APT). Micrometer-sized hematite platelets were reacted with aqueous Fe(II) enriched in 57Fe and prepared for APT using conventional focused ion beam lift-out techniques. Mass spectrum analyses show that specific Fe-ionic species (i.e., Fe2+ and FeO+) accurately reproduce isotopic ratios within natural abundance in the hematite bulk, and thus were utilized to characterize the distribution of 57Fe and quantify Fe isotopic concentrations. 3D reconstructions of Fe isotopic positions along the surface normal direction showed a zone enriched in 57Fe, consistent with oxidative adsorption of Fe(II) and growth at the relict hematite surface reacted with 57Fe(II)aq. An average net adsorption of 3.2–4.3 57Fe atoms nm–2 was estimated using Gibbsian interfacial excess princip...
Modeling the interactions of sense and antisense Period transcripts in the mammalian circadian clock network

In recent years, it has become increasingly apparent that antisense transcription plays an important role in the regulation of gene expression. The circadian clock is no exception: an antisense transcript of the mammalian core-clock gene PERIOD2 (PER2), which we shall refer to as Per2AS RNA, oscillates with a circadian period and a nearly 12 h phase shift from the peak expression of Per2 mRNA. In this paper, we ask whether Per2AS plays a regulatory role in the mammalian circadian clock by studying in silico the potential effects of interactions between Per2 and Per2AS RNAs on circadian rhythms. Based on the antiphasic expression pattern, we consider two hypotheses about how Per2 and Per2AS mutually interfere with each other's expression. In our pre-transcriptional model, the transcription of Per2AS RNA from the non-coding strand represses the transcription of Per2 mRNA from the coding strand and vice versa. In our post-transcriptional model, Per2 and Per2AS transcripts form a double-stranded RNA duplex, which is rapidly degraded. To study these two possible mechanisms, we have added terms describing our alternative hypotheses to a published mathematical model of the molecular regulatory network of the mammalian circadian clock. Our pre-transcriptional model predicts that transcriptional interference between Per2 and Per2AS can generate alternative modes of circadian oscillations, which we characterize in terms of the amplitude and phase of oscillation of core clock genes. In our post-transcriptional model, Per2/Per2AS duplex formation dampens the circadian rhythm. In a model that combines pre- and post-transcriptional controls, the period, amplitude and phase of circadian proteins exhibit non-monotonic dependencies on the rate of expression of Per2AS. All three models provide potential explanations of the observed antiphasic, circadian oscillations of Per2 and Per2AS RNAs. They make discordant predictions that can be tested experimentally in order to distinguish among these alternative hypotheses.
Abstract 17396: Effect of Donor Troponin on Heart Transplant Outcomes: A UNOS Registry Analysis

Introduction: Heart transplantation is the treatment of choice for end stage heart failure, but is limited to approximately 4000 globally every year due to donor shortage. Despite this, only one-third of the potential donor hearts are recovered for transplantation. Although elevated donor troponin levels have generally been considered a contraindication, the data supporting this practice is limited. Hypothesis: Elevated donor troponins in the presence of normal left ventricular ejection fraction (LVEF) do not impact outcomes after transplantation. Methods: All adult heart transplant recipients in the UNOS database between 2007 and 2014, with LVEF≥50%, and reported donor troponin I levels were included. The overall cohort was divided into groups based on clinically meaningful troponin I levels: below 1, 1-10, 10.1-20 and above 20 and compared for recipient survival and coronary allograft vasculopathy (CAV). Results: 11,640 transplants met the study criteria. On comparison of baseline characteristics, higher troponin groups had younger donors and greater donor CPR. Importantly, the ischemic time and proportion of recipients in the ICU and on temporary circulatory support were similar. As shown, there was no difference in survival (figure 1) or CAV (figure 2) up to 5 years of follow up using Kaplan-Meir analysis and cox-hazards ratio. After adjusting for differences in baseline covariates and clinically relevant factors, the findings remained unchanged. Conclusions: In this largest analysis to date, elevated donor troponin levels in the setting of preserved LVEF did not impact recipient survival or CAV up to 5 years of follow up. This finding can help expand the donor pool.
Liraglutide Modulates Appetite and Body Weight Through Glucagon-Like Peptide 1 Receptor–Expressing Glutamatergic Neurons

Glucagon-like peptide 1 receptor (GLP-1R) agonists are U.S. Food and Drug Administration–approved weight loss drugs. Despite their widespread use, the sites of action through which GLP-1R agonists (GLP1RAs) affect appetite and body weight are still not fully understood. We determined whether GLP-1Rs in either GABAergic or glutamatergic neurons are necessary for the short- and long-term effects of the GLP1RA liraglutide on food intake, visceral illness, body weight, and neural network activation. We found that mice lacking GLP-1Rs in vGAT-expressing GABAergic neurons responded identically to controls in all parameters measured, whereas deletion of GLP-1Rs in vGlut2-expressing glutamatergic neurons eliminated liraglutide-induced weight loss and visceral illness and severely attenuated its effects on feeding. Concomitantly, deletion of GLP-1Rs from glutamatergic neurons completely abolished the neural network activation observed after liraglutide administration. We conclude that liraglutide activates a dispersed but discrete neural network to mediate its physiological effects and that these effects require GLP-1R expression on glutamatergic but not GABAergic neurons.
Miniaturized Positioners for Modular Packaging

The most radical mechanical change in present-day airborne electronic equipment, especially in military systems, is modular packaging. A radio package designed for today’s aircraft is composed of stacked, functional modules, each plugged into a common base which supplies both electrical connections and cooling air. These modules, each a complete chassis with its own functions, performance requirements, and electronic capabilities, are major subdivisions of the electronic system. The sizes of these modules are standardized to permit their use as building blocks in the equipment construction.
Association Between Simulation Curriculum and Learners' Confidence and Interest in Cardiothoracic Surgery

This study examines the use of tissue-based simulations in cardiothoracic surgery with medical students, residents, and fellows.
Pericardial Effusion, Tamponade, and Constriction

Normally, the intrapericardial space between the two pericardial layers contains 25–50mL serous fluid secreted by the visceral pericardium and the intrapericardial pressure is equal to the intrapleural pressure. The pericardium provides mechanical protection for the heart and lubrication to reduce friction between the heart and contiguous structures. Because of the relative lack of distensibility, the pericardium also exerts hemodynamic impact on cardiac function. It limits acute distention of the heart and contributes to diastolic interaction between the two ventricles (the distention of one ventricle affects the filling dynamics of the other).
Association Between Midlife Risk Factors and Late-Onset Epilepsy: Results From the Atherosclerosis Risk in Communities Study.

Importance The incidence of epilepsy is higher in older age than at any other period of life. Stroke, dementia, and hypertension are associated with late-onset epilepsy; however, the role of other vascular and lifestyle factors remains unclear. Objective To identify midlife vascular and lifestyle risk factors for late-onset epilepsy. Design, Setting, and Participants The Atherosclerosis Risk in Communities (ARIC) study is a prospective cohort study of 15 792 participants followed up since 1987 to 1989 with in-person visits, telephone calls, and surveillance of hospitalizations (10 974 invited without completing enrollment). The ARIC is a multicenter study with participants selected from 4 US communities. This study included 10 420 black or white participants from ARIC with at least 2 years of Medicare fee-for-service coverage and without missing baseline data. Data were analyzed betweeen April 2017 and May 2018. Exposures Demographic, vascular, lifestyle, and other possible epilepsy risk factors measured at baseline (age 45-64 years) were evaluated in multivariable survival models including demographics, vascular risk factors, and lifestyle risk factors. Main Outcomes and Measures Time to development of late-onset epilepsy (2 or moreInternational Classification of Diseases, Ninth Revision codes for epilepsy or seizures starting at 60 years or older in any claim [hospitalization or outpatient Medicare through 2013]), with first code for seizures after at least 2 years without code for seizures. Results Of the 10 420 total participants (5878 women [56.4%] and 2794 black participants [26.8%]; median age 55 years at first visit), 596 participants developed late-onset epilepsy (3.33 per 1000 person-years). The incidence was higher in black than in white participants (4.71; 95% CI, 4.12-5.40 vs 2.88; 95% CI, 2.60-3.18 per 1000 person-years). In multivariable analysis, baseline hypertension (hazard ratio [HR], 1.30; 95% CI, 1.09-1.55), diabetes (HR, 1.45; 95% CI, 1.17-1.80), smoking (HR, 1.09; 95% CI, 1.01-1.17), apolipoprotein E e4 genotype (1 allele HR, 1.22; 95% CI, 1.02-1.45; 2 alleles HR, 1.95; 95% CI, 1.35-2.81), and incident stroke (HR, 3.38; 95% CI, 2.78-4.10) and dementia (HR, 2.56; 95% CI, 2.11-3.12) were associated with an increased risk of late-onset epilepsy, while higher levels of physical activity (HR, 0.90; 95% CI, 0.83-0.98) and moderate alcohol intake (HR, 0.72; 95% CI, 0.57-0.90) were associated with a lower risk. Results were similar after censoring individuals with stroke or dementia. Conclusions and Relevance Potentially modifiable risk factors in midlife and the APOE e4 genotype were positively associated with risk of developing late-onset epilepsy. Although stroke and dementia were both associated with late-onset epilepsy, vascular and lifestyle risk factors were significant even in the absence of stroke or dementia.
Cytocoded passwords: BioMEMS based barcoding of biological samples for user authentication in microfluidic diagnostic devices

Smart and connected point-of-care (POC) medical devices are becoming ever more ubiquitous and have the potential to radically improve disease diagnosis and health monitoring. This emerging connectivity can potentially create serious security issues where patient privacy can be easily compromised. Protection of patient data from malicious cyber-physical attackers requires radical solutions at the BioMEMS level. Ideally, the information exchange between the patient and practitioner is an automated and transparent process for the patient. In practice, this exchange requires both the patient and the test results to be authenticated and validated respectively on the storage service to ensure that the medical diagnostic results are properly stored and their access is protected. This secure authentication phase is particularly critical for medical diagnostics: patient data exposure could lead to negative social effects. This work focuses on providing a transparent authentication mechanism for patient blood tests performed using impedance flow cytometry. The goal is twofold: first, to alleviate the user from security procedures, precisely an authentication step, while using the medical device; second, to provide a unique identifier for the test results when stored in a remote server. This paper describes a domain specific authentication method for impedance flow cytometry devices. We spike into the blood samples synthetic micro-beads of different sizes, at determined concentrations, to generate a unique authentication string that uniquely identify a test result on the remote storage service. These authentication strings are embedded in the test devices and can be used as a convenient alternative to generic authentication methods, such as logins and passwords. This alternative method removes the authentication burden from the user and protects patient’s privacy further by preventing them from linking their personal information to their test results.
Tuning the Electrochemical Redox Potentials of Catechol with Boronic Acid Derivatives

A strategy to control the oxidation potential of catechol using borinic acids is presented. Borinic acids reversibly bind catechol to form boron “ate” complexes (BACs) that alter the electron density on the oxygen atoms of catechol and, in turn, the propensity of the catechol toward electrochemical oxidation. The effect of different substituents on the borinic acid are investigated to determine their efficacy in tuning the electron density within the BAC and the resulting oxidation potential.
An investigation of single-domain and multidomain medication and adverse drug event relation extraction from electronic health record notes using advanced deep learning models.

OBJECTIVE We aim to evaluate the effectiveness of advanced deep learning models (eg, capsule network [CapNet], adversarial training [ADV]) for single-domain and multidomain relation extraction from electronic health record (EHR) notes. MATERIALS AND METHODS We built multiple deep learning models with increased complexity, namely a multilayer perceptron (MLP) model and a CapNet model for single-domain relation extraction and fully shared (FS), shared-private (SP), and adversarial training (ADV) modes for multidomain relation extraction. Our models were evaluated in 2 ways: first, we compared our models using our expert-annotated cancer (the MADE1.0 corpus) and cardio corpora; second, we compared our models with the systems in the MADE1.0 and i2b2 challenges. RESULTS Multidomain models outperform single-domain models by 0.7%-1.4% in F1 (t test P < .05), but the results of FS, SP, and ADV modes are mixed. Our results show that the MLP model generally outperforms the CapNet model by 0.1%-1.0% in F1. In the comparisons with other systems, the CapNet model achieves the state-of-the-art result (87.2% in F1) in the cancer corpus and the MLP model generally outperforms MedEx in the cancer, cardiovascular diseases, and i2b2 corpora. CONCLUSIONS Our MLP or CapNet model generally outperforms other state-of-the-art systems in medication and adverse drug event relation extraction. Multidomain models perform better than single-domain models. However, neither the SP nor the ADV mode can always outperform the FS mode significantly. Moreover, the CapNet model is not superior to the MLP model for our corpora.
Examining a Syndemics Network Among Young Latino Men Who Have Sex with Men

Although studies consistently find that syndemic indicators are additively associated with increased HIV/STI risk behavior (e.g., condomless anal sex; CAS) among men who have sex with men (MSM), information is lacking about how syndemic indicators are associated with each other. Young Latino MSM are one of the most at-risk groups for acquiring HIV in the U.S. Understanding the associations of syndemic indicators with each other and with CAS may improve understanding of how to enhance sexual and behavioral health in this population. Network analysis using the graphical LASSO (glasso) algorithm was employed to explore associations between CAS and syndemic indicators among 139 young Latino MSM. Structural and psychosocial syndemic indicators were assessed via self-report. CAS was defined as the number of partners in the past 3 months with whom one engaged in CAS. Results of the network analysis suggested the variables with the highest centrality were unstable housing, prison history, childhood sexual abuse, and CAS. Specific significant associations included links between CAS and alcohol use (b = 0.40), childhood sexual abuse and unstable housing (b = − 0.75), alcohol use and childhood sexual abuse (b = 0.40), and substance use and intimate partner violence (b = 0.43). This pattern of interconnectedness demonstrates the potential for network analysis to examine nuanced interrelationships of syndemic indicators. The specific associations in this sample raise the question whether a primary focus of interventions should address the more central syndemic indicators for this population, such as alcohol use and unstable housing, and whether this would, via downstream effects, affect other aspects of behavioral health in this population.
Simulation modeling of complex climate, wildfire, and vegetation dynamics to address wicked problems in land management

Complex, reciprocal interactions among climate, disturbance, and vegetation dramatically alter spatial landscape patterns and influence ecosystem dynamics. As climate and disturbance regimes shift, past analogs and empirical studies may not be entirely appropriate as templates for future management. The need for a better understanding of the potential impacts of climate changes on ecosystems is reaching new levels of urgency, especially in highly perturbed or vulnerable ecological systems that challenge implementation of effective management strategies. Simulation models are extremely useful tools for guiding management decisions in an era of rapid change, thus providing potential solutions for wicked problems in land management—those that are difficult to solve and inherently resistant to easily definable solutions. We identify three experimental approaches for landscape modeling that address management challenges in the context of uncertain climate futures and complex ecological interactions: (1) an historical comparative approach, (2) a future comparative approach, and (3) threshold detection. We provide examples of each approach from previously published studies of simulated climate, disturbance, and landscape dynamics in forested landscapes of the western United States, modeled with the FireBGCv2 ecosystem process model. Cumulatively, model outcomes indicate that typical land management strategies will likely not be sufficient to counteract the impacts of rapid climate change and altered disturbance regimes that threaten the stability of ecosystems. Without implementation of new, adaptive management strategies, future landscapes are very likely to be different than historical or contemporary ones, with significant and sometimes persistent changes triggered by interactions of climate and wildfire.
The prevalence of the gout-associated polymorphism rs2231142 G>T in ABCG2 in a pregnant female Filipino cohort.

Gout is a metabolic disorder and one of the most common arthritic conditions. Hyperuricemia is the hallmark of developing gout and mostly caused by uric acid underexcretion. Gout disproportionately affects people of specific races and ethnicities. Filipinos are the second-largest Asian population in the USA and reported to have a higher prevalence of gout and hyperuricemia than non-Filipino counterparts and Filipinos residing in the Philippines. The genetic polymorphism rs2231142 G>T in the ABCG2 has been strongly associated with hyperuricemia and gout across multiple populations. However, the prevalence of this variant in Filipinos is unknown. Therefore, assessing the prevalence of this variant may provide insights on the high prevalence of hyperuricemia and gout in Filipinos. A total of 190 DNA samples from pregnant females who self-identified as a Filipino from the Hawaii Biorepository Bank were genotyped for rs2231142 G>T in the ABCG2. The prevalence of the gout risk allele (T) (46%) was significantly higher in Filipinos than in samples of Caucasians (12%, p < 0.001), Han Chinese (29%, p = 0.014), and African Americans (3%, p < 0.001). Similarly, the prevalence of the gout-risk genotype (TT) (21%) was significantly higher in Filipinos than in samples of Caucasians (1%, p < 0.001), Han Chinese (9%, p = 0.002), and African Americans (0.1%, p < 0.001). Though there were no gout cases in this cohort, these findings are suggestive of a genetic basis to the high prevalence of hyperuricemia and gout in Filipinos. This might also explain the reported reduced urinary uric acid excretion in Filipinos compared with Caucasians.
A Tutorial on VAEs: From Bayes' Rule to Lossless Compression

The Variational Auto-Encoder (VAE) is a simple, efficient, and popular deep maximum likelihood model. Though usage of VAEs is widespread, the derivation of the VAE is not as widely understood. In this tutorial, we will provide an overview of the VAE and a tour through various derivations and interpretations of the VAE objective. From a probabilistic standpoint, we will examine the VAE through the lens of Bayes' Rule, importance sampling, and the change-of-variables formula. From an information theoretic standpoint, we will examine the VAE through the lens of lossless compression and transmission through a noisy channel. We will then identify two common misconceptions over the VAE formulation and their practical consequences. Finally, we will visualize the capabilities and limitations of VAEs using a code example (with an accompanying Jupyter notebook) on toy 2D data.
Redesigning Water Disinfection Using Recyclable Nanomaterials and Metal Ions: Evaluation with Escherichia coli

We present a novel disinfection method that redesigns the conventional approach, by recycling the disinfectant. This can lead to lower energy requirements and minimize environmental impacts. In thi...
Female Socialization: How Daughters Affect Their Legislator Fathers

Parenting daughters, sociologists have shown, increases feminist sympathies. I test the hypothesis that children, much like neighbors or peers, can influence parental behavior. I demonstrate that conditional on total number of children, each daughter increases a congressperson's propensity to vote liberally, particularly on reproductive rights issues. The results identify an important (and previously omitted) explanatory variable in the literature on congressional decision making. Additionally the paper highlights the relevance of child-to-parent behavioral influence. (JEL D72, D83, J16)
Optical control of ferroelectric switching and multifunctional devices based on van der Waals ferroelectric semiconductors

Indium Selenide (In2Se3) is a newly emerged van der Waals (vdW) ferroelectric material, which unlike traditional insulating ferroelectric materials, is a semiconductor with a bandgap of about 1.36 eV. Ferroelectric diodes and transistors based on In2Se3 have been demonstrated. However, the interplay between light and electric polarization in In2Se3 has not been explored. In this paper, we found that the polarization in In2Se3 can be programmed by optical stimuli, due to its semiconducting nature, where the photo generated carriers in In2Se3 can alter the screening field and lead to polarization reversal. Utilizing these unique properties of In2Se3, we demonstrated a new type of multifunctional device based on 2D heterostructures, which can concurrently serve as a logic gate, photodetector, electronic memory and photonic memory. This dual electrical and optical operation of the memories can simplify the device architecture and offer additional functionalities, such as ultrafast optical erase of large memory arrays. In addition, we show that dual-gate structure can address the partial switching problem commonly observed in In2Se3 ferroelectric transistors, as the two gates can enhance the vertical electric field and facilitate the polarization switching in the semiconducting In2Se3. These discovered effects are of general nature and should be observable in any ferroelectric semiconductor. These findings deepen the understanding of polarization switching and light-polarization interaction in semiconducting ferroelectric materials and open up their applications in multifunctional electronic and photonic devices.