cssi/SciSciGPT-SciSciNet huggingface dataset:
Resistance of ‘Gaucho’ Triticale to Schizaphis graminum

‘Gaucho’ (CI 15323) is an octoploid Triticale developed from a cross between susceptible ‘Chinese Spring’ common wheat and an Argentine rye (Insave F. A.) that is resistant to the greenbug, Schizaphis graminum (Rondani). (Insave F. A. is the only greenbug-resistant rye known at present.) Arriaga and Ree (1963) reported that a single dominant gene controlled the overall resistance in this rye to the greenbug. The transfer of resistance to common wheat would be of great importance to wheat production since no practical level of resistance is present in commercial varieties. However, the chromosomes of rye rarely pair with those of wheat in the intergeneric hybrid, so the transfer of desirable characteristics from rye to wheat by conventional breeding methods is impossible (Riley and Chapman 1958). However, a number of workers have used an irradiation technique to obtain transfer of genetic material carrying genes for disease resistance via alien chromosomes to wheat (Sears 1967). Therefore, the transfer of greenbug resistance from the Argentine rye via Gaucho to wheat should be possible since only one of the pairs of rye chromosomes bears the genes for resistance.
Depression and the Performance of Masculinity in a Military Retirement Community

Depression can be viewed as a psychiatric illness and, as a folk ideology, part of the conceptual world of everyday life for many people. In public culture, ideas about depression are often associa...
Expression of nuclear factor-erythroid 2-related factor 2 and cytochrome C in premature newborn rats' lung exposed to hyperoxia and their significance

Objective To observe the expression of nuclear factor-erythroid 2-related factor 2( Nrf2) and Cytochrome C( Cytc) in premature newborn rats exposed to hyperoxia,and explore the role of Nrf2 and Cytc level changes in hyperoxia lung injury. Methods One-day old preterm SD rats were randomly into two groups: hyperoxia group and air group. Hyperoxia group were continuously exposed to oxygen( oxygen 0. 85) and air group in room air. After 1,4,7,10,14 days of exposure,the preterm SD rats of two groups were killed,whole lung of these rats were isolated,lung histological changes were observed by hematoxylin-eosin staining( HE). Total lung RNA was extracted,Nrf2 and Cytc mRNA were detected by reverse transcription polymerase chain reaction( RT-PCR). Results The results showed that: ① Compaired with air group,the expression of nuclear factor-erythroid 2-related factor 2( Nrf2) in lung tissue induced hyperoxia significantly increased after 4,7 days of exposure( P 0. 05),the general tendency decreased after 10 days,but the expression of Nrf2 became significantly weak after 14 days of exposure( P 0. 05). ②Compaired with air group,the expression of Cytc mRNA were significantly increased in 1,4 days of hyperoxia group( P 0. 05),the general tendency decreased after 7 days, but its expression still mildly increased in 7 day and became weak in 10 day of hyperoxia group,but there was no significant difference between two groups in 7,10 days( P 0. 05),the expression of Cytc mRNA became significantly weaker than its expression after 14 days of air group( P 0. 05). Conclusion Oxidation outbreak resulted in the abnormal expression of nuclear factor-erythroid 2-related factor 2( Nrf2) and Cytc in the lung of premature SD rats exposed to hyperoxia,these changes participated in the development of hyperoxia induced lung injury,the activity of Nrf2 may be increased by hyperoxia exposure,and alleviate hyperoxia lung injury through antioxidation of Nrf2,and Cytc played an important role in the process of cell apoptosis in hyperoxia lung injury.
Visas brew trouble for US science

"Mother of Mercy, is this the end of Rico?" – Edward G Robinson in Little Caesar (1931). As the gangster Rico Bandello observed in amazement as he glanced at his bullet-riddled body, all good things come to an end. Empires tumble to whispered expressions of schadenfreude. Such is the fear of the US research and education communities.
More on Numerical Methods for Unconstrained Optimum Design

Advanced topics related to unconstrained optimization methods are presented. Step size calculation by polynomial interpolation is described. Inexact step size calculation is discussed using Armijo’s rule and Wolfe conditions. Properties of the gradient vector in the context of the steepest descent method are discussed. It is shown that the successive steepest descent directions are orthogonal to each other. Scaling of design variables to improve rate of convergence of the steepest descent method is discussed. The Newton method for search direction calculation is presented, and Marquardt’s modification is discussed. The quasi-Newton methods for search direction calculation are presented and illustrated. Some engineering applications of unconstrained optimization methods are presented. Solution of constrained optimization problems using the sequential unconstrained optimization methods is described, such as the barrier methods, penalty methods, and the augmented Lagrangian methods. Rate of convergence of iterative sequences generated by the optimization algorithms is discussed. Two direct search methods that do not require gradients of the function are presented and discussed.
Structuring Symbolic Interaction: Communication and Power

The basic stance of symbolic interaction as developed by Blumer is presented. Recent writings on power, complex organization, negotiations, mass media, social problems, strategic analysis, and alig...
The Debate About Electronic Cigarettes: Harm Minimization or the Precautionary Principle.

Two contrasting reviews (authored by Abrams et al. and Glanz & Bareham) in this volume have reached opposing conclusions on the effects of electronic cigarettes in a debate that is dividing the scientific and professional communities that have devoted careers to controlling the manufacture, advertising, sale, and use of combustible cigarettes. The research on the types, degree, and extent of harm from e-cigarettes is far from complete and, together with trends in teenage smoking and vaping, has raised new questions and prospects about the potential benefits that the new electronic products offer smokers of combustible cigarettes in quitting or at least cutting back on the known risks associated with the traditional forms of smoking. The rapidly morphing forms, constituents, promotions, and uses of the electronic varieties of the new nicotine delivery products (in this case electronic cigarettes) make research on their biological and behavioral effects moving targets. The two sides of this argument have pr...
Development and evaluation of a variably saturated flow model in the global E3SM Land Model (ELM) version 1.0

Abstract. Improving global-scale model representations of near-surface soil moisture and groundwater hydrology is important for accurately simulating terrestrial processes and predicting climate change effects on water resources. Most existing land surface models, including the default E3SM Land Model (ELMv0), which we modify here, routinely employ different formulations for water transport in the vadose and phreatic zones. Clark et al. (2015) identified a variably saturated Richards equation flow model as an important capability for improving simulation of coupled soil moisture and shallow groundwater dynamics. In this work, we developed the Variably Saturated Flow Model (VSFM) in ELMv1 to unify the treatment of soil hydrologic processes in the unsaturated and saturated zones. VSFM was tested on three benchmark problems and results were evaluated against observations and an existing benchmark model (PFLOTRAN). The ELMv1-VSFM's subsurface drainage parameter, fd , was calibrated to match an observationally constrained and spatially explicit global water table depth (WTD) product. Optimal spatially explicit fd values were obtained for 79 % of global 1.9 ∘ × 2.5 ∘ grid cells, while the remaining 21 % of global grid cells had predicted WTD deeper than the observationally constrained estimate. Comparison with predictions using the default fd value demonstrated that calibration significantly improved predictions, primarily by allowing much deeper WTDs. Model evaluation using the International Land Model Benchmarking package (ILAMB) showed that improvements in WTD predictions did not degrade model skill for any other metrics. We evaluated the computational performance of the VSFM model and found that the model is about 30 % more expensive than the default ELMv0 with an optimal processor layout. The modular software design of VSFM not only provides flexibility to configure the model for a range of problem setups but also allows for building the model independently of the ELM code, thus enabling straightforward testing of the model's physics against other models.
Classical Concrete Problems

The overwhelming majority of functional relations encountered in mathematics and its applications are non-linear ‘in the large’ but linear ‘in the small’. For example the linear theory of elasticity is founded on the assumption that stresses depend linearly on deformations when the latter are small. The method of mathematical analysis, which is firmly established in the works of Newton and Leibniz, consists of two basic procedures:
How Professional and Regulatory Bodies Facilitate Quality Management: An Analysis Using the Cascaded House of Quality

This article demonstrates the use of the cascaded house of quality for professional and regulatory bodies. It discusses ways by which regulatory bodies can mitigate problems arising from information asymmetry between customers and product and service pr..
In-Vehicle Affect Detection System: Identification of Emotional Arousal by Monitoring the Driver and Driving Style

There have been clear needs to address the impact of driver emotions such as anger and happiness on aggressive or distracted driving behaviors. To tackle this issue, we have developed an affect detection system for identifying a driver's emotional arousal, including the driver's physiological data and vehicle's kinematic data. Multimodal sensors are wirelessly connected to a smartphone and then, all the driver and driving data are displayed on our Android application in real-time. With the benefits of this multimodal, portable, non-intrusive, and cost-efficient system, subsequent experiments were designed to test and improve the system. After identifying significant features, various machine learning algorithms will be used to model a driver's emotional states. Our final goal is to develop an optimized classifier of specific emotional states including arousal and valence. We hope that we can spark lively discussions on driver emotions at AutoUI and use the feedback to improve our system.
Abstract TP213: Retinal Microvascular Abnormalities as Markers of Cerebrovascular Disease: A Meta-Analysis

Introduction: Despite the recognized linkage between retinal microvascular abnormalities and cerebrovascular ischemic diseases (CVD), the retinal findings’ standardization and the degree of associa...
Human EGFR-2, EGFR and HDAC triple-inhibitor CUDC-101 enhances radiosensitivity of GBM cells

Radiotherapy remains the standard treatment for glioblastoma multiforme (GBM) following surgical resection. Given the aberrant expression of human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor (EGFR) which may play a role in therapeutic resistance to receptor tyrosine kinase inhibitors, and the emerging use of histone deacetylase (HDAC) inhibitors as radiosensitizers, we defined the effects of CUDC-101, a triple inhibitor of HER2, EGFR and HDAC on the radiosensitivity of GBM cells. Clonogenic survival was used to determine the in vitro radiosensitizing potential of CUDC-101 on GBM, breast cancer, and normal fibroblast cell lines. Inhibitory activity was defined using immunoblots and DNA double strand breaks were evaluated using yH2AX foci. Effects of CUDC-101 on cell cycle and radiation-induced cell kill were determined using flow cytometry and fluorescent microscopy. CUDC-101 inhibited HER2, EGFR and HDAC and enhanced in vitro radiosensitivity of both GBM and breast cancer cell lines, with no effect on normal fibroblasts. Retention of yH2AX foci was increased by CUDC-101 alone and in combination with irradiation for 24 h. Treatment with CUDC-101 increased the number of cells in G2 and M phase, with only increase in M phase statistically significant. An increase in mitotic catastrophe was seen in a time-dependent fashion with combination treatment. The results indicate the tumor specific CUDC-101 enhanced radiosensitization in GBM, and suggest that the effect involves inhibition of DNA repair.
Physical Chemistry of Cellular Liquid‐Phase Separation

Compartmentalization of biochemical processes is essential for cell function. Although membrane-bound organelles are well studied in this context, recent work has shown that phase separation is a key contributor to cellular compartmentalization through the formation of liquid-like membraneless organelles (MLOs). In this Minireview, the key mechanistic concepts that underlie MLO dynamics and function are first briefly discussed, including the relevant noncovalent interaction chemistry and polymer physical chemistry. Next, a few examples of MLOs and relevant proteins are given, along with their functions, which highlight the relevance of the above concepts. The developing area of active matter and non-equilibrium systems, which can give rise to unexpected effects in fluctuating cellular conditions, are also discussed. Finally, our thoughts for emerging and future directions in the field are discussed, including in vitro and in vivo studies of MLO physical chemistry and function.
Clinical Impact of Protamine Titration-Based Heparin Neutralization in Patients Undergoing Coronary Bypass Grafting Surgery

Objectives A hemostasis management system (HMS) is a point-of-care method for heparin and protamine titration. The authors hypothesized that protamine dosing over the HMS estimate would be associated with elevated activated clotting time (ACT), increased bleeding, and transfusion owing to protamine's anticoagulant activity. Design A retrospective cohort study. Setting Single-center university hospital. Participants One hundred eighty-nine patients undergoing elective coronary artery bypass grafting surgery. Interventions Patients were stratified into 3 groups per ratio of actual total administered protamine versus the HMS-derived protamine estimate: (1) low-ratio (≤66% of HMS estimate), (2) moderate-ratio (66%-100% of HMS estimate), and (3) high-ratio (>100% of HMS estimate). Measurements and Main Results The primary endpoints were post-protamine ACT, and residual heparin levels on HMS among the 3 groups in addition to bleeding and transfusion. There were 54 (28.6%) patients in the low, 95 (50.3%) in the moderate, and 40 (21.2%) in the high-ratio group. The high-ratio patients who were overdosed with protamine relative to the HMS estimate had elevated ACT, international normalized ratio, and activated partial thromboplastin time values, and subsequently received more red blood cell (RBC) and non-RBC transfusions compared to lower-ratio groups. Higher actual/HMS protamine ratios were associated independently with post-protamine ACT elevations after adjustment for sex, body mass index (BMI), and cardiopulmonary bypass (CPB) time. Conclusion Most patients received the protamine dose sufficiently close to the HMS estimate, but protamine dosing above the HMS estimate occurred in both obese and nonobese patients, which was associated independently with prolonged ACT after adjusting for sex, BMI, and CPB time.
Systems approaches to urban planning: Mixed, conditional, adaptive and other alternatives

Systems approaches possess an ability to deal with large numbers of interacting variables and relations. They are here connected tocitizen information systems (distinguished frommanagement information systems) and to mixed, adaptive, conditional models for urban planning. The latter permit flexible and continuing responses to dynamically changing urban conditions, including citizen attitudes and reactions, as well as to changing economics and technologies. These models are “mixed” in that they allow actions and reactions from a multiplicity of decisionmakers. The resulting decisions are made only conditionally, rather than once-and-for-all, on a comprehensive basis as in the customary “master city plan.” Proceeding in this conditional manner, the model then permits adaptation to changing values and objectives as, at each stage, it makes the systems consequences apparent. The systems approach is related to a host of important methodological developments in mathematics, statistics, etc., as well as in electronic computers and their use. These distinguish modern systems approaches from predecessors like the “holism” of Jan Christiaan Smuts and others in pre-war science. The mixed, conditional, adaptive models suggested here are compared with other approaches like “advocacy planning,” the “comprehensive master city plan” and “ad hoc planning.” It is found to be possible at least in principle, to accommodate all of these and even to extend matters further to include day-to-day as well as longer range facilities plans in the indicated systems approach by virtue of the improved methodologies that may now be used or developed for these purposes.
Characterization of Phosphoranes Obtained by the Spontaneous Carbonyl-Catalyzed Phosphorylation of Monosaccharides and Polyols in Aqueous Media

Phosphorylation is a very important biochemical process in metabolism and biochemical marking. The mechanism for the biophosphorylation of substrates and the hydrolysis/transesterification of RNA has been suggested to proceed through phosphorane intermediates. Although the phosphorane intermediate/transition state has long been a subject of many theoretical models and studies, it has neither been isolated nor characterized, with most information derived from the hydrolysis and radiolabeling of cyclic phosphotriesters. We herein present the first report of the spontaneous phosphorylation of sugars and polyols in the absence of enzymes. That is, aldehydes and ketones combine with inorganic phosphates to form activated phosphates that phosphorylate alcohols without the requirement of any enzyme or additional activating agent. This phosphorylation is particularly favored in polyhydroxycarbonyls that can form internal cyclic acetals to give rise to the corresponding acetal phosphoranes. We have further characterized these phosphoranes and demonstrated their dehydration to the corresponding phosphates by using high-resolution mass spectroscopy. The phosphorylation of adenosine and uridine to form the corresponding phosphoranes was also achieved.
Efficient Real-Time Digital Subcarrier Cross-Connect (DSXC) Based on Distributed Arithmetic DSP Algorithm

Two real-time functions of digital subcarrier cross-connect (DSXC) are experimentally demonstrated for the first time using distributed arithmetic (DA) in a field programmable gate array (FPGA) platform. Both frequency translation and channel selection in DSXC are implemented using DA-based resampling filters, achieving flexible modulation format and fine data-rate granularity of many concurrent subcarrier channels. Compared with traditional resampling filters that leverage multipliers, the DA-based approach eliminates the need for DSP slices in the FPGA implementation and significantly reduces the hardware cost. By requiring only a few clock periods, the DA-based resampling filter is also significantly faster when compared to conventional FIR filters, whose overall latency is proportional to the filter order. The DA-based DSXC is therefore able to achieve improved spectral efficiency and programmability of multiple orthogonal subcarrier channels, while keeping low cross-connection latency and requiring low cost hardware resources when implemented in a FPGA platform.
Factors Limiting Behavioral Research in Accounting

The objective of this note is to caution against expecting golden eggs from a normal goose. It ts probably easier for those who have not actually conducted behavioral research to build high expectations for its policy use and implications simply because it appears the obvious way to do ex ante research, i.e., prior to making the final standards. Behavioral research methods have their own promises as well as weaknesses. The message I intend to emphasize in this note is the need for triangulation in research; that is, multiplicity of research methods of which behavioral methods are only a component. Furthermore, almost by necessity, policy relevant research is one that generates concordant findings simply because policies and standards generate their own strength from being generally acceptable.
Cyclophosphamide-induced cystitis results in NLRP3-mediated inflammation in the hippocampus and symptoms of depression in rats

Recent breakthroughs demonstrate that peripheral diseases can trigger inflammation in the brain, causing psychosocial maladies, including depression. While few direct studies have been made, anecdo...
Segmenting retinal OCT images with inter-B-scan and longitudinal information

Monitoring retinal thickness of persons with multiple sclerosis (MS) provides important bio-markers for disease progression. However, changes in retinal thickness can be small and concealed by noise in the acquired data. Consistent longitudinal retinal layer segmentation methods for optical coherence tomography (OCT) images are crucial for identifying the real longitudinal retinal changes of individuals with MS. In this paper, we propose an iterative registration and deep learning based segmentation method for longitudinal 3D OCT scans. Since 3D OCT scans are usually anisotropic with large slice separation, we extract B-scan features using 2D deep networks and utilize inter-B-scan context with convolutional long-short-term memory (LSTM). To incorporate longitudinal information, we perform fundus registration and interpolate the smooth retinal surfaces of the previous visit to use as a prior on the current visit.
Optimal Control for Cancer Chemotherapy under Tumor Heterogeneity

Designing an effective chemotherapeutic treatment for cancer is of practical interest, and challenging due to the mutation between tumor cells and tumor heterogeneity. Recent studies, in the areas of systems science and engineering, have modeled the cancer cell population as a dynamic system and thus the chemotherapeutic treatment can be considered as the control acts on this population. In this model, tumor heterogeneity, which is the main obstacle that complicates the dynamics of the cancer cell population, can be characterized by the cell’s drug-resistance levels. As a result, an optimal ensemble control problem can be formulated to minimize the combination of tumor volumes and drugs’ side effects, which guarantees the effectiveness of the designed treatment. In this work, we extend our studies on optimal control for cancer chemotherapy by considering the mutations between cells. We first briefly describe the corresponding mathematical model, and then derive the optimal treatment protocols for such a cancer cell population. Several numerical examples are included to illustrate the impact of mutations and discuss the optimal cancer treatment scenarios.
Inlets and sampling

Abstract When transferring an analytical method from one-dimensional to multidimensional gas chromatography (MDGC), certain parameters require special attention. Here, the sample preparation (SP) and sample introduction are usually the least considered. However, even the most advanced MDGC approach is incapable of compensating for poor SP and injection. Therefore, a reevaluation of these analytical steps is certainly useful when methods are transferred to MDGC. This chapter provides a brief overview of the basic principles and applications of SP and introduction techniques commonly applied in MDGC. In addition, the effects of these techniques on the chromatographic process and the analytical results are discussed. The considerations presented here are intended to provide helpful information for beginners in MDGC.
TRPV1 Tunes Optic Nerve Axon Excitability in Glaucoma.

The transient receptor potential vanilloid member 1 (TRPV1) in the central nervous system may contribute to homeostatic plasticity by regulating intracellular Ca2+, which becomes unbalanced in age-related neurodegenerative diseases, including Alzheimer's and Huntington's. Glaucomatous optic neuropathy - the world's leading cause of irreversible blindness - involves progressive degeneration of retinal ganglion cell (RGC) axons in the optic nerve through sensitivity to stress related to intraocular pressure (IOP). In models of glaucoma, genetic deletion of TRPV1 (Trpv1-/- ) accelerates RGC axonopathy in the optic projection, whereas TRPV1 activation modulates RGC membrane polarization. In continuation of these studies, here, we found that Trpv1-/- increases the compound action potential (CAP) of optic nerves subjected to short-term elevations in IOP. This IOP-induced increase in CAP was not directly due to TRPV1 channels in the optic nerve, because the TRPV1-selective antagonist iodoresiniferatoxin had no effect on the CAP for wild-type optic nerve. Rather, the enhanced CAP in Trpv1-/- optic nerve was associated with increased expression of the voltage-gated sodium channel subunit 1.6 (NaV1.6) in longer nodes of Ranvier within RGC axons, rendering Trpv1-/- optic nerve relatively insensitive to NaV1.6 antagonism via 4,9-anhydrotetrodotoxin. These results indicate that with short-term elevations in IOP, Trpv1-/- increases axon excitability through greater NaV1.6 localization within longer nodes. In neurodegenerative disease, native TRPV1 may tune NaV expression in neurons under stress to match excitability to available metabolic resources.
Palliative care knowledge and self-awareness in active and observing undergraduate nursing students after end-of-life simulation.

Aim: The purpose of this quasi-experimental one-group repeated measure (pre-test/post-test) study was to determine the effect of an end-of-life (EoL) simulation-based experience (SBE) on active and...
The gut–brain axis mediates sugar preference

The taste of sugar is one of the most basic sensory percepts for humans and other animals. Animals can develop a strong preference for sugar even if they lack sweet taste receptors, indicating a mechanism independent of taste1–3. Here we examined the neural basis for sugar preference and demonstrate that a population of neurons in the vagal ganglia and brainstem are activated via the gut–brain axis to create preference for sugar. These neurons are stimulated in response to sugar but not artificial sweeteners, and are activated by direct delivery of sugar to the gut. Using functional imaging we monitored activity of the gut–brain axis, and identified the vagal neurons activated by intestinal delivery of glucose. Next, we engineered mice in which synaptic activity in this gut-to-brain circuit was genetically silenced, and prevented the development of behavioural preference for sugar. Moreover, we show that co-opting this circuit by chemogenetic activation can create preferences to otherwise less-preferred stimuli. Together, these findings reveal a gut-to-brain post-ingestive sugar-sensing pathway critical for the development of sugar preference. In addition, they explain the neural basis for differences in the behavioural effects of sweeteners versus sugar, and uncover an essential circuit underlying the highly appetitive effects of sugar. Experiments in mice show that a population of neurons in the vagal ganglia respond to the presence of glucose in the gut and connect to neurons in the brainstem, revealing the circuit that underlies the neural basis for the behavioural preference for sugar.
Losing the wait: improving patient cycle time in primary care.

Inefficient clinic systems leading to prolonged wait times at primary care clinics are a source of frustration for patients, physicians, staff and administration. Measuring and shortening cycle time has the potential to improve patient experience, staff satisfaction and patient access by moving more patients through in a shorter cycle time. Limited studies have demonstrated that improvements can be made to cycle time and may result in improved patient satisfaction. Most of these studies have focused their efforts on improving efficiency at the front end of the cycle. Our aim was to improve cycle time for the whole visit to less than 60 min within 1 year by engaging our team in brainstorming solutions, presenting regular measurements to our team for review and holding regular meetings to plan rapid improvement cycles. Over the course of 1 year (2017), we were able to reduce cycle time by 12% from 71 to 65 min and to improve patient satisfaction with care. Despite the reduction in cycle time, we maintained high satisfaction scores from patients who felt that the doctor spent enough time with them. We learnt the value of engaging our team, frequent measurement for reporting, adequate staffing at the beginning of clinic, and the value of MA staff acting in a flow coordinator role. We have not only maintained this improvement but also made further small gains over the subsequent 2 years, and by April 2019, our cycle time is at 60 min, despite a marked increase in patient volume. Additional work on the time after the patient is roomed and waiting for a doctor, and further analysis of the physician workflow would be important next steps to drive further improvement.
GSK3-ARC/Arg3.1 and GSK3-Wnt signaling axes trigger amyloid-β accumulation and neuroinflammation in middle-aged Shugoshin 1 mice.

The cerebral amyloid-β accumulation that begins in middle age is considered the critical triggering event in the pathogenesis of late-onset Alzheimer's disease (LOAD). However, the molecular mechanism remains elusive. The Shugoshin 1 (Sgo1-/+ ) mouse model, a model for mitotic cohesinopathy-genomic instability that is observed in human AD at a higher rate, showed spontaneous accumulation of amyloid-β in the brain at old age. With the model, novel insights into the molecular mechanism of LOAD development are anticipated. In this study, the initial appearance of cerebral amyloid-β accumulation was determined as 15-18 months of age (late middle age) in the Sgo1-/+ model. The amyloid-β accumulation was associated with unexpected GSK3α/β inactivation, Wnt signaling activation, and ARC/Arg3.1 accumulation, suggesting involvement of both the GSK3-Arc/Arg3.1 axis and the GSK3-Wnt axis. As observed in human AD brains, neuroinflammation with IFN-γ expression occurred with amyloid-β accumulation and was pronounced in the aged (24-month-old) Sgo1-/+ model mice. AD-relevant protein panels (oxidative stress defense, mitochondrial energy metabolism, and β-oxidation and peroxisome) analysis indicated (a) early increases in Pdk1 and Phb in middle-aged Sgo1-/+ brains, and (b) misregulations in 32 proteins among 130 proteins tested in old age. Thus, initial amyloid-β accumulation in the Sgo1-/+ model is suggested to be triggered by GSK3 inactivation and the resulting Wnt activation and ARC/Arg3.1 accumulation. The model displayed characteristics and affected pathways similar to those of human LOAD including neuroinflammation, demonstrating its potential as a study tool for the LOAD development mechanism and for preclinical AD drug research and development.
PARP Inhibitors in Metastatic Prostate Cancer: Evidence to Date

Poly (ADP-ribose) polymerase inhibitors (PARPi) are a unique class of antineoplastic agents that function by inducing synthetic lethality. Synthetic lethality occurs when PARPi and either another agent or an underlying genetic alteration together lead to overwhelming DNA damage and ultimately cell death. PARPi first showed promise as a cancer therapy in patients with BRCA1/2 mutations and have become part of standard treatment for breast and ovarian cancer. In prostate cancer, two PARPi, rucaparib and olaparib, have been FDA approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC). While both agents are approved for tumors with BRCA1/2 alterations, for olaparib the indication is also expanded to patients with 12 other homologous recombination deficiency (HRD) gene alterations including ATM and PALB2. PARPi differ in their pharmacokinetics and pharmacodynamics, and additional studies are being conducted with niraparib, veliparib, and talazoparib in prostate cancer. While PARPi are fairly well tolerated, common toxicities include hematologic (anemia/thrombocytopenia) and gastrointestinal effects (nausea/vomiting). Ongoing studies are being conducted combining PARPi with other agents in patients with and without HRD alterations. Early data are promising for the combination of PARPi with second-generation antiandrogens and with immunotherapy. As additional trials are developed and reported, the hope is that the patient population who may benefit from PARPi will continue to expand.
Longitudinal assessment of Lung Clearance Index as a marker of disease progression in a cohort of children with cystic fibrosis and normal spirometry

Objectives: The lung clearance index at 2.5 of starting concentration (LCI2.5) from Nitrogen multiple breath washout (MBW) has demonstrated sensitivity to early lung disease in Cystic Fibrosis (CF). Our study aims to evaluate if the LCI2.5 can identify lung disease progression in children with CF with normal lung function by spirometry. Methods: We have enrolled 57 children with CF (mean age 10.3 + 3, range 6 - 18 years; 22 boys, 35 girls) into a longitudinal study that evaluates spirometry, MBW and patient reported outcomes at clinical encounters. Our main endpoint is FEV1 decline over one year. Results: At baseline these children demonstrated normal parameters (mean FVC 99.2 + 20 %-pred., FEV1 94 + 21 %-pred., FEV1/FVC ratio 0.84 + 0.12; BMI 61 + 24 %-ile), with no significant differences between boys and girls (p > 0.25 for all). However, by LCI there was evidence for airway disease (Mean 9.4 units + 2.6) and with no differences between boys and girls (p = 0.5). At baseline modest correlation was found between LCI and FEV1%-pred. (r 0.45, p = 0.001). During follow up, on average no significant change in FEV1 was noted (p = 0.57). However, there was an inverse correlation between baseline LCI and FEV1 decline (-2.5 %-pred./year for every unit of LCI2.5, p= 0.0001) and between change in LCI2.5 and FEV1 decline (-2.0 %-pred./year for every unit of increase in LCI2.5, p Conclusion: The LCI2.5 from MBW identifies children with subsequent decline in FEV1. One unit increase in LCI seems to be a strong indicator of lung disease activity. Funding Source: US CFF MILLA17A0
Consolidating Emergency Department-specific Data to Enable Linkage with Large Administrative Datasets.

Introduction: The American Hospital Association (AHA) has hospital-level data, while the Centers for Medicare & Medicaid Services (CMS) has patient-level data. Merging these with other distinct databases would permit analyses of hospital-based specialties, units, or departments, and patient outcomes. One distinct database is the National Emergency Department Inventory (NEDI), which contains information about all EDs in the United States. However, a challenge with merging these databases is that NEDI lists all US EDs individually, while the AHA and CMS group some EDs by hospital network. Consolidating data for this merge may be preferential to excluding grouped EDs. Our objectives were to consolidate ED data to enable linkage with administrative datasets and to determine the effect of excluding grouped EDs on ED-level summary results.Methods: Using the 2014 NEDI-USA database, we surveyed all New England EDs. We individually matched NEDI EDs with corresponding EDs in the AHA and CMS. A “group match” was assigned when more than one NEDI ED was matched to a single AHA or CMS facility identification number. Within each group, we consolidated individual ED data to create a single observation based on sums or weighted averages of responses as appropriate.Results: Of the 195 EDs in New England, 169 (87%) completed the NEDI survey. Among these, 130 (77%) EDs were individually listed in AHA and CMS, while 39 were part of groups consisting of 2-3 EDs but represented by one facility ID. Compared to the individually listed EDs, the 39 EDs included in a “group match” had a larger number of annual visits and beds, were more likely to be freestanding, and were less likely to be rural (all P<0.05). Two grouped EDs were excluded because the listed ED did not respond to the NEDI survey; the remaining 37 EDs were consolidated into 19 observations. Thus, the consolidated dataset contained 149 observations representing 171 EDs; this consolidated dataset yielded summary results that were similar to those of the 169 responding EDs.Conclusion: Excluding grouped EDs would have resulted in a non-representative dataset. The original vs consolidated NEDI datasets yielded similar results and enabled linkage with large administrative datasets. This approach presents a novel opportunity to use characteristics of hospital-based specialties, units, and departments in studies of patient-level outcomes, to advance health services research.
Effect of the cooling rate in solidification on the electrical behavior of solder

Solder is widely used for electrical interconnections in electronics, and its use involves the melting and subsequent solidification of the solder. This paper reports for the first time the effect of the cooling rate in solidification on the electrical behavior (conduction and dielectric behavior) of the solidified solder. Prior work addressed the effect of the cooling rate on the microstructure and mechanical properties only. The solder is Sn-4Ag (lead free, melting temperature 221 °C). Cooling is from the melt at 230 °C. Comparison of the cooling rates corresponding to air cooling and ice-water quenching indicates that the microstructure is much finer and the resistivity (DC) is higher by 2.4% for the quenching case. However, the permittivity (100 kHz) is the same for the two cooling rates. This means that the microstructural refinement associated with the quenching decreases the mobility without affecting the carrier–atom interaction responsible for the permittivity. The carriers are the valence electrons. Since the polarization associated with the permittivity involves the interaction of a fraction of the valence electrons with the atoms, this further implies that the fraction of carriers that interact with the atoms is not affected by the microstructural refinement and that the decrease in mobility (as indicated by the resistivity increase) does not affect this fraction. The fractional increase in the resistivity due to the quenching (relative to air cooling) during solidification (this work) is small compared to that due to the mild heating of the solid solder to 70 °C (our prior work). The mild heating also does not affect the permittivity.
TLR2 on CD4+ and CD8+ T cells promotes late control of Mycobacterium tuberculosis infection

Abstract Although a role for TLR2 on T cells has been indicated in prior studies, in vivo stimulation of TLR2 on T cells by Mtb and its impact on Mtb infection has not been tested. Furthermore, it is not known if the enhanced susceptibility to Mtb of Tlr2 gene knockout (ko) mice is due to its role in macrophages, on T cells or both. To address TLR2 on T cells, we generated Tlr2fl/flxCd4cre/cre mice, which lack expression of TLR2 on both CD4 and CD8 T cells, to study the in vivo role of TLR2 on T cells after aerosol infection with virulent Mtb. Deletion of TLR2 in CD4+ and CD8+ T cells reduces their ability to be co-stimulated by TLR2 ligands for cytokine production. These include both pro-(IFN-γ, TNF-α) and anti-inflammatory cytokines (IL-10). Deletion of TLR2 in T cells did not affect early control but did result in decreased late control of Mtb in the lungs of infected mice. This suggests that T cell co-stimulation by mycobacterial TLR2 ligands in vivo is important for control of infection during the chronic phase of Mtb infection in the lung.
To the Defeated Belong the Spoils: France and the Haitian Independence Debt

In 1804 Haiti declared its independence from France, after defeating French forces in a twelve-year long slave insurrection turned revolutionary war. Two decades later, France finally agreed to recognize Haitian statehood on the condition that Haiti pay a substantial indemnity to compensate French colonists for their losses from the Haitian Revolution. To the victor belong the spoils, or so the saying goes. So why was the nascent Haitian nation made to foot the bill for France’s defeat twenty-one years earlier by paying French property owners? And might Haiti have a legal claim to restitution of its debt? This article attempts to answer these questions, and in doing so, it interrogates the limitations of international law as a means for redressing colonial-era harms.
Between Mess and Method: Performance Art Economix/tures

Between Mess and Method: Performance Art Economix/tures will draw on a decade of cultural organizing framed as performance art by performance artists and cultural activists in New York City (USA). Using examples such as the “imaginary institution” Brooklyn International Performance Art Foundation, Esther Neff parses and describes methodological and practical tactics devised and developed particularly by queer, trans, GNB/GNC feminists* in the USA to support “our own” work and dismantle extractive, coercive, capitalist cultural economies.
Genetically Polymorphic Cytochrome P450s and Transporters and Personalized Antimicrobial Chemotherapy

This chapter summarizes a number of functionally important genetic polymorphisms in drug-metabolizing enzymes and drug transporters and their genotyping methodologies, by which individuals susceptible to drug toxicity or loss of efficacy can be identified or predicted easily in the clinical setting. The human cytochrome P450 (CYP) enzyme system contributing to drug metabolism comprises the CYP families CYP1, CYP2, and CYP3. Among these CYPs, proteins encoded by the human CYP3A genes catalyze the metabolism of nearly half of all currently used drugs, and approximately 40% of all marketed drugs are substrates for CYP2C9, CYP2C19, and CYP2D6. Moreover, the CYP2B6, CYP2C9, CYP2C19, and CYP2D6 enzymes exhibit large variations in the levels of their protein expression and enzymatic activity as a result of frequently occurring, functionally important genetic polymorphisms. Typically, in addition to passive diffusion, a drug is transported into cells by uptake (or influx) transporters, such as organic anion transporters (OATs), organic anion transport peptides (OATPs), and organic cation transporters (OCTs), whereas the drug and its metabolite(s) are removed from the cells by efflux transporters, such as P-glycoprotein (P-gp), multidrug resistance proteins (MRPs), and breast cancer resistance protein (BCRP). Anti-infective drugs may be substrates for some uptake transporters, drug-metabolizing enzymes, and efflux transporters.
Human sexual selection

Sexual selection favors traits that aid in competition over mates. Widespread monogamous mating, biparental care, moderate body size sexual dimorphism, and low canine tooth dimorphism suggest modest sexual selection operating over human evolution, but other evidence indicates that sexual selection has actually been comparatively strong. Ancestral men probably competed for mates mainly by excluding competitors by force or threat, and women probably competed primarily by attracting mates. These and other forms of sexual selection shaped human anatomy and psychology, including some psychological sex differences.
The spectral analysis of stationary interval functions

We consider stationary. additive. interval functions X(Δ). These are vector valued stochastic processes having real intervals Δ = (α, β] as domain, having finite dimensional distributions invariant under time translation and satisfying
Evidence on Indirect Bankruptcy Costs: Liquidation Rates, Opportunity Costs, and the Value of Intertemporal Asset Storage

The present paper examines bankrupt firm liquidation data with duration, OLS and three-stage least squares models to estimate the costs and benefits of bankruptcy liquidation delays. The paper uses Federal Deposit Insurance Corporation data on failed banks to estimate net present value maximizing liquidation strategies while keeping holdout effects, forum shopping, and debt renegotiation constant. Lengthy liquidations can impose high opportunity costs, but these costs can be substantially mitigated by asset appreciation over the liquidation period. Therefore it is important to simultaneously weigh the costs and benefits of delay. The NPV-maximizing liquidation strategy may therefore not always be the fastest.
Limited Arbitrage and Uniqueness of Equilibrium in Strictly Regular Economies

In strickly regular economies limited arbitrage is sufficient for the global invertibility of demand, and necessary and sufficient for the uniqueness of equilibrium. This result is established using algevraic topology and holds in economies with short sales, and with finitely or infinitely many markets.
Squamous cell carcinoma of the penis: Evaluation of data from the surveillance, epidemiology, and end results program

BACKGROUND Penile carcinoma is uncommon. Therefore, obtaining meaningful epidemiologic data requires analysis of large, multisource databases. The authors examined the association between different demographic variables and the prevalence, presentation, and survival of patients with penile squamous cell carcinoma in the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database. METHODS The SEER database represents 12% of the U.S. population. The database included 1605 patients with a diagnosis of penile squamous cell carcinoma between 1973 and 1998. The variables analyzed were age, race, marital status, stage at presentation, type of surgery, performance of lymphadenectomy, and disease-specific survival. RESULTS Of 1605 patients, 37% presented with carcinoma in situ (CIS), 39% with localized disease, 13% with regional disease, 2.3% with distant disease, and 7.9% of the patients were unstaged. The percentage of patients presenting with CIS and localized disease increased and decreased yearly, respectively. African Americans represented 9.9% of the population and tended to present at a younger age and with a higher stage of disease, and their cancer-specific survival was shorter in all stages. However, these associations were statistically significant only for men with regional disease. Marital status was documented for 1394 patients (87%). The majority (84%) had a history of marriage and presented at an earlier stage of disease and had higher disease-specific survival in the localized (P = 0.0002) and regional stages (P = 0.0010) of disease. CONCLUSIONS The diagnosis of penile carcinoma significantly reduced survival. African-American men presented with a higher stage of disease and statistically significant decreased survival, whereas previously or currently married men presented at an earlier stage of disease and sought more aggressive treatment. Cancer 2004. © 2004 American Cancer Society.
A Test Suite Generation Method for Extended Finite State Machines Using Axiomatic Semantics Approach

In this paper, a test suite generation method is proposed for conformance testing of communication protocols. We try to solve a challenging problem: generating test sequences for protocol specification models that contain memories. A program verification technique, called axiomatic semantics, is used to test protocols specified by extended finite state machines (EFSMs). While an EFSM is symbolically verified, observable events are recorded. By carefully manipulating the execution path in the EFSM, the observed events can be used to examine whether or not protocol implementations are in conformance with their specifications.