cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract 693: Oncogenic and osteolytic function of histone demethylase NO66 in castration resistant prostate cancer

Androgen ablation by pharmacological use or castration is a standard therapy for treating prostate cancer (PCa), however, at the later stage PCa becomes castration-resistant and is metastasized primarily to bones. Epigenetic changes that cause dysregulated gene expression during progression and metastasis of androgen-independent prostate cancer are not clearly understood. We previously reported that the jumonji C domain-containing NO66 is a histone demethylase specific for H3K4me3 and H3K36me3, which negatively regulates osteoblast differentiation and bone formation. By analyzing a multi-cancer tissue microarray, the serendipitous observation was made that NO66 is overexpressed in a variety of cancers. Our objective was to examine NO669s role in the pathogenesis of prostate cancer and bone metastasis. Our findings indicate that NO66 knockdown resulted in significant decreases in the proliferation and invasiveness of prostate cancer cells (PC3 and DU145) while overexpressing NO66 promoted their proliferation and invasion. Furthermore, NO66 depletion resulted in a two- to three fold decrease in colony formation and anchorage-independent growth of PCa cells suggesting an oncogenic function of NO66. RNAseq analysis comparing between control and NO66-depleted DU-145 cells revealed a repertoire of differentially expressed genes. NO66 up-regulates genes with proliferative activity such as chemokine CXCL5, growth factor IGFBP5, IL6, WNT and MAPK4 pathway, which are known to drive PCa proliferation. Furthermore, ChIP sequencing for NO66 and H3K9AC in NO66-overexpressing PC3 cells revealed that interaction sites of NO66 overlap with peaks of H3K9AC in majority of the genes. These data clearly indicate that NO66 activates a cohort of genes which are involved in tumor progression and metastasis. Strikingly, implanting NO66-overexpressing prostate cancer cells into the femur of SCID male mice caused massive femoral bone loss after three weeks, which suggests that NO66 causes osteolytic bone lesions similar to the clinico-pathological features of advanced PCa. Finally, analysis of tumor xenografts derived from patients by immunohistochemistry showed high expression of NO66 in high grade advanced PCa compared to low grade and hyperplasia suggesting that NO66 may be used as a biomarker to distinguish aggressive prostate cancer from indolent stage. Our data suggest that NO66 plays an important role in cell proliferation, cell invasion and bone metastasis of prostate cancer. Citation Format: Rozita Bagheri-Yarmand, Nora Navone, Xinhai Wan, Christopher Logothetis, Johnny Huard, Krishna Sinha. Oncogenic and osteolytic function of histone demethylase NO66 in castration resistant prostate cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 693.
Examination of Blog Discussion about the Beheading of Two American Journalists by ISIS

This study utilizes the beheading of two American journalists, James Foley and Steven Sotloff by Islamic State of Iraq and Syria (ISIS) in 2014. The content analyses of 980 comments from three political blogs (Townhall - conservative, Daily Kos - liberal, and The Moderate Voice - moderate) reveal that the majority of blog users exhibited their subjective thoughts and opinions rather than engaging in deliberative communication based on deep reasoning. Blog users also did not show a reciprocal attitude, mostly ignoring different voices. Most comments were made based on one-sided perspectives.
Human Resources for Treating HIV/AIDS: Are the Preventive Effects of Antiretroviral Treatment a Game Changer?

Shortages of human resources for treating HIV/AIDS (HRHA) are a fundamental barrier to reaching universal antiretroviral treatment (ART) coverage in developing countries. Previous studies suggest that recruiting HRHA to attain universal ART coverage poses an insurmountable challenge as ART significantly increases survival among HIV-infected individuals. While new evidence about ART’s prevention benefits suggests fewer infections may mitigate the challenge, new policies such as treatment-as-prevention (TasP) will exacerbate it. We develop a mathematical model to analytically study the net effects of these countervailing factors. Using South Africa as a case study, we find that contrary to previous results, universal ART coverage is achievable even with current HRHA numbers. However, larger health gains are possible through a surge-capacity policy that aggressively recruits HRHA to reach universal ART coverage quickly. Without such a policy, TasP roll-out can increase health losses by crowding out sicker patients from treatment, unless a surge capacity exclusively for TasP is also created.
An Innovative Use of Cortoss Bone Cement to Stabilize a Nonunion after Interbody Fusion

A 65-year-old male originally had surgery for spondylolisthesis at L5-S1 in 2008 and then went on to have an L4-5 transforaminal lumbar interbody fusion (TLIF) with pedicle screw fixation from L4 to S1 and interbody graft in 2010. Despite having two surgical procedures, he continued with intractable back pain and was told he had a failed lumbar fusion. When he was evaluated with a computerized tomography (CT) scan from April 2015, it demonstrated an erosive nonunion of the L4-5 interbody fusion without incorporation of the polyetheretherketone (PEEK) cage. In an attempt to perform a minimally invasive stabilization of the L4-5 nonunion, he underwent a percutaneous lateral foraminal approach with an injection of Cortoss® cement (Stryker®, Malvern, PA) into the L4-5 interspace and around the graft. The objective was to stabilize the nonunion, resulting in intermediate relief of pain.
Rust-like borrowing with 2nd-class values (short paper)

The Rust programming language demonstrates that memory safety can be achieved in a practical systems language, based on a sophisticated type system that controls object lifetimes and aliasing through notions of ownership and borrowing. While Scala has traditionally targeted only managed language runtimes, the ScalaNative effort makes Scala a viable low-level language as well. Thus, memory safety becomes an important concern, and the question bears asking what, if anything, Scala can learn from Rust. In addition, Rust's type system can encode forms of protocols, state machines, and session types, which would also be useful for Scala in general. A key challenge is that Rust's typing rules are inherently flow-sensitive, but Scala's type system is not. In this paper, we sketch one possible method of achieving static guarantees similar to Rust with only mild extensions to Scala's type system. Our solution is based on two components: First, the observation that continuation passing style (CPS) or monadic style can transform a flow-sensitive checking problem into a type-checking problem based on scopes. Second, on a previously presented type system extension with second-class values, which we use to model scope-based lifetimes.
S36. DIFFERENTIAL ENCODING OF SENSITIZATION AND CROSS SENSITIZATION TO PSYCHOSTIMULANTS AND ANTIPSYCHOTICS IN NUCLEUS ACCUMBENS D1- AND D2- RECEPTOR EXPRESSING MEDIUM SPINY NEURONS

AbstractBackgroundNearly half of all individuals diagnosed with schizophrenia abuse addictive substances such as cocaine. Currently, the neurobiological mechanisms in patients with schizophrenia that lead to cocaine abuse are unknown. A possible explanation for the co-morbidity between schizophrenia and addiction is that the rewarding properties of cocaine reverse the diminished motivational drive caused by chronic antipsychotic regimen. Moreover, chronic antipsychotic treatment can sensitize and amplify cocaine rewarding effects and exacerbate psychoses.MethodsThe rewarding properties of cocaine are attributed to the differential effects of dopamine on D1 and D2 receptor-expressing medium spiny neurons (MSNs) in the nucleus accumbens (NAc). Using in vivo Ca2+ miniature microscopic imaging, we characterize the role of D1 and D2 MSN in mono- and a cross- sensitization paradigms. D1- and D2-Cre mice were injected with a Cre dependent calcium indicator (gCaMP6f) and implanted with a gradient index (GRIN) lens above the nucleus accumbens and calcium activity was recorded using a head mounted miniature microscope. Cocaine sensitization was measured after a classic repeated cocaine regiment and antipsychotic and psychostimulant cross-sensitization was measured by a single cocaine injection after chronic pre-treatment with haloperidol.ResultsWe found that both D1-MSN and D2-MSN populations are modulated by initial cocaine experience and further modulated during the expression of cocaine sensitization. A subpopulation of D1-MSN displayed initial activation, but reduced activity during the expression of sensitization. By contrast, the majority of D2-MSNs were suppressed by initial cocaine experience, but became active during the expression of sensitization. Furthermore, activity of D1- and D2-MSNs bidirectionally related with the observed behavioral responses to cocaine. Cross-sensitization following haloperidol treatment led to increased behavioral responses to psychostimulants. Current experiments are set out to investigate the neuronal responses of D1 and D2-MSN during cross sensitization between haloperidol and cocaine.DiscussionCocaine sensitization leads to differential neuronal responses in D1- and D2-MSN and these responses are differentially correlated with the magnitude of the sensitized behavioral response. These results reveal important new insights in the neurobiological processes in the nucleus accumbens that underlie psychostimulant sensitization and provide an important new model for studying the pharmacology of antipsychotic effects on striatal function and its potential role in increasing the susceptibility of schizophrenic patients to developing drug addiction.
Clival Malformations in CHARGE Syndrome.

BACKGROUND AND PURPOSE: CHARGE syndrome is a multisystemic congenital disorder, most commonly including coloboma, heart malformations, choanal atresia, developmental delay, and genital and ear anomalies. The diagnostic criteria for CHARGE syndrome have been refined with time. However, limited reports describe skull base and craniocervical junction abnormalities. Recently, a coronal clival cleft has been identified in association with CHARGE syndrome. The aim of our study was to assess the prevalence of clival pathology in CHARGE syndrome. MATERIALS AND METHODS: In this retrospective study, the CT/MR imaging data base at a single academic children9s hospital was queried for the phrase “CHARGE syndrome” during a 17-year period (2001–2017). Electronic medical records were reviewed to confirm the diagnosis. Images were assessed for skull base anomalies, specifically clival hypoplasia and dysplasia. RESULTS: The search yielded 42 examinations (21 CTs and 21 MRIs) from 15 distinct patients (mean age, 4.1 ± 5.6 years; range, 2 days to 19 years). CHARGE syndrome diagnosis was confirmed either by clinical and genetic testing ( n = 6) or by clinical diagnosis only ( n = 9). A coronal clival cleft was identified in 87% of patients (37 examinations, n = 13 patients), either partial (53%) or complete (33%). Clival hypoplasia without clefting was present in all 5 examinations from the remaining 2 patients. CONCLUSIONS: Clival pathology is universal in CHARGE syndrome. Coronal clival clefts are extremely common, representing a useful additional diagnostic finding. Detection of a clival cleft should alert the radiologist to examine the palate, choana, eyes, ears, and olfactory centers for other signs of CHARGE syndrome.
First Rib Resection and Thoracoscopic Cervical Sympathectomy

Idiopathic hyperhidrosis (excessive sweating) is a common benign condition that may cause a patient significant social, emotional, and professional distress. By definition, hyperhidrosis is the secretion of sweat in amounts greater than physiologically needed for thermoregulation. Diagnosis consists of focal, visible, excessive sweating of at least 6 months duration without apparent cause with at least two of the following criteria: Bilateral and relatively symmetric Impairs daily activities At least one episode per week Onset before age 25 Family history of idiopathic hyperhidrosis Focal sweating stops during sleep
Control of muscle synergies by cortical ensembles

Since its introduction in the early 1980s, the concept of a “preferred direction” for neuronal discharge has proven to be a powerful means of studying diverse properties of individual neurons in the motor areas of the brain. More recently, the activity recorded from ensembles of neurons, each with an identified preferred direction, has been used to predict hand movement, both off-line, and in real-time. Our recent experiments have addressed similar issues, but have focused on the relation between primary motor cortical discharge and muscle activity, rather than limb kinematics.
Role of aminoacyl-tRNA synthetases in infectious diseases and targets for therapeutic development.

Aminoacyl-tRNA synthetases (AARSs) play a pivotal role in protein synthesis and cell viability. These 22 “housekeeping” enzymes (1 for each standard amino acid plus pyrrolysine and o-phosphoserine) are specifically involved in recognizing and aminoacylating their cognate tRNAs in the cellular pool with the correct amino acid prior to delivery of the charged tRNA to the protein synthesis machinery. Besides serving this canonical function, higher eukaryotic AARSs, some of which are organized in the cytoplasm as a multisynthetase complex of nine enzymes plus additional cellular factors, have also been implicated in a variety of non-canonical roles. AARSs are involved in the regulation of transcription, translation, and various signaling pathways, thereby ensuring cell survival. Based in part on their versatility, AARSs have been recruited by viruses to perform essential functions. For example, host synthetases are packaged into some retroviruses and are required for their replication. Other viruses mimic tRNA-like structures in their genomes, and these motifs are aminoacylated by the host synthetase as part of the viral replication cycle. More recently, it has been shown that certain large DNA viruses infecting animals and other diverse unicellular eukaryotes encode tRNAs, AARSs, and additional components of the protein-synthesis machinery. This chapter will review our current understanding of the role of host AARSs and tRNA-like structures in viruses and discuss their potential as anti-viral drug targets. The identification and development of compounds that target bacterial AARSs, thereby serving as novel antibiotics, will also be discussed. Particular attention will be given to recent work on a number of tRNA-dependent AARS inhibitors and to advances in a new class of natural “pro-drug” antibiotics called Trojan Horse inhibitors. Finally, we will explore how bacteria that naturally produce AARS-targeting antibiotics must protect themselves against cell suicide using naturally antibiotic resistant AARSs, and how horizontal gene transfer of these AARS genes to pathogens may threaten the future use of this class of antibiotics.
A Brief History of 30 Years of Model Updating in Structural Dynamics

Since the development of the Finite Element (FE) method at the University of California Berkeley and the Boeing Company in the 1960s, the question of appropriateness of a model has always preoccupied developers and practicing engineers. Because of the early focus on predicting the linear vibrations of coupled systems for aerospace and civil engineering applications, test-analysis reconciliation initially consisted in updating the FE matrices such that their eigen-properties reproduce the identified resonant frequencies and mode shape vectors. As the FE method increased in sophistication in the following decades, and computational resources became widespread, test-analysis reconciliation evolved beyond optimal matrix updating to include sensitivity and residual-based methods that attempted to calibrate individual element matrices or design parameters. Fueled by an ever-increasing diversity of applications, FE model updating expanded beyond the correlation of modal response to handle frequency response functions, static deflections, and time-domain waveforms. Component mode synthesis concepts were progressively integrated to handle the spatial mismatch between measurement points of a structure and the FE discretization where the spatial information is predicted. This publication briefly overviews the first 30 years of FE model updating development, from the mid-1960s to the mid-1990s, because most of the technology currently available originates in this period. FE model updating methods are categorized into broad categories that each offer their own benefits and limitations. Potential growth areas, such as application to nonlinear dynamics, are discussed.
Signaling in Trypanosoma cruzi

Many signaling pathways known to be present in metazoans are also present in unicellular organisms, and Trypanosoma cruzi is not an exception. T. cruzi shares key molecules and biochemical pathways with higher eukaryotes. For example, calcium, adenylyl cyclase, guanylyl cyclase, phospholipase C, nitric oxide synthase, protein kinases, and protein serine/threonine and tyrosine phosphatases, were all found to play central roles in T. cruzi. However, current evidence suggest that T. cruzi might lack some molecules involved in signaling such as receptor-linked phospholipases, protein kinases and phosphatases, heterotrimeric G proteins, and transcription factors necessary for regulation of gene expression.
Decisions about Reproduction: Genetic Counseling

Recent advances in human genetics and medicine have increased our understanding of genetic disorders and have enabled us to participate in reproductive decision making and behavior. The chemical structure of DNA and the underlying biochemical mechanism for many hereditary disorders are understood. Tissue culture techniques permit cells to be grown and analyzed, both biochemically and cytogenetically, in laboratories. Many genetic disorders that result in birth defects are amenable to surgical correction. Specific chromosome abnormalities, many inborn errors of metabolism, and some birth defects can now accurately be detected in utero, with little risk to mother or fetus. Genetic counseling services have expanded, and the ability to detect genetic defects in asymptomatic carriers of mutant genes has increased. Genetic screening programs, implemented in many communities, have gradually increased public awareness of problems of heredity. This cumulative increase in theory and practice constitutes a quantum leap in knowledge.
Regulation of the Immune Response by the Fc Portion of Immunoglobulin

Abstract The Fc portion of mammalian Ig possesses the ability to augment in vivo and in vitro specific antibody responses and in vitro T cell-mediated immune responses. Enhancement of specific antibody responses occurs only when thymus-dependent antigens are employed. Although Fc fragments do not induce T cells to proliferate, they enhance antigen and allogeneic cell-induced proliferation. In both cases the cell population that is acted upon by Fc fragments bears the Lyt 1 + 2 - phenotype. In addition, Fc fragments potentiate the primary CML response. In order for Fc to augment MLC and CML responses, an I-A and/or I-B H-2 region difference must exist between the stimulator and responder cell populations.
Residential electricity demand in Taiwan: Consumption behavior and rebound effect

Abstract The residential electricity demand in Taiwan was investigated using survey data of 7677 households between 2014 and 2017. Right-skewed regression models were employed to study key determinants affecting the household and appliance-specific electricity consumption. Appliances covered air conditioner, lighting, television, and refrigerator. The difference of electricity consumption between appliances with and without energy efficiency label was also studied; thus rebound effects were obtained. The estimated results indicate that household income, indoor floor area, and owning the house had positive influences on electricity consumption. Electricity consumption behavior was different among age groups and appliances. Moreover, rebound effect was large for air conditioner and refrigerator in Taiwan.
Abstract TP166: Frequency of Brain Death in Acute Cerebrovascular Disease Related Mortality

Background: Despite the frequent occurrence of brain death in intensive care unit, the prevalence rate of brain death in ischemic stroke (IS), intracranial hemorrhage (ICH) and subarachnoid hemorrh...
Multifunction acoustic modulation by a multi-mode acoustic metamaterial architecture

Exotic acoustical features, like acoustic transparency, ultrasonic beam focusing, acoustic band gap and super lensing capability using a single metamaterial architecture is unconventional and unprecedented in the literature, demonstrated herein. Conventional metamaterials can focus an ultrasonic beam at specific frequency which results into unwanted distortion of the output wave fields at neighboring sonic frequencies in the host medium. However, ultrasonic wave focusing by virtue of negative refraction and simultaneous transparency of the metamaterial at sonic frequencies are uncommon due to their frequency disparity. To circumvent this problem and to avoid the unwanted distortion of wave at sonic frequencies, metamaterial with an array of butterfly-shaped thin ring resonators are proposed to achieve the beam focusing at ultrasonic frequency (37.3 kHz) and keep the structure transparent to the sonic frequencies (<20 kHz). The butterfly metamaterial with local ring resonators or butterfly crystals (BC) were previously proposed to create wide band gaps (~7 kHz) at ultrasonic frequencies above 20 kHz. However, in this study a unique sub-wavelength scale wave focusing capability of the butterfly metamaterial utilizing the negative refraction phenomenon is demonstrated, while keeping the metamaterial block transparent to the propagating wave at lower sonic frequencies below the previously reported bandgaps.
Dual Language and English-Only Learners' Expressive and Receptive Language Skills and Exposure to Peers' Language

This study examined dual language learners' (DLLs n = 24) and English-only (EO n = 20) children's expressive and receptive language in kindergarten (Mage = 5.7 years) as well as the relation to peers' language use. Expressive language skills (vocabulary diversity, syntactic complexity) were measured in the fall, winter, and spring (2014-2015 year). Receptive language skills (vocabulary, sentence comprehension) were measured in the fall and spring. Findings revealed increases in children's expressive and receptive language, except in terms of syntactic complexity. Moreover, peers' vocabulary diversity was positively associated with children's vocabulary diversity. Peers' syntactic complexity was positively associated with children's syntactic complexity and receptive vocabulary. Findings suggest that peers' language use may influence DLLs' and EO children's language learning. [ABSTRACT FROM AUTHOR]
The crisis of policy education in turbulent times: Are schools of public affairs in danger of becoming irrelevant?

ABSTRACTThe work of crafting sustainable solutions to complex policy problems requires decision makers and implementers to secure buy-in from a diverse set of stakeholders. Those stakeholders opera...
Understanding the mechanical link between oriented cell division and cerebellar morphogenesis

The cerebellum is a tightly folded structure located at the back of the head. Unlike the folds of the cerebrum, the folds of the cerebellum are aligned such that the external surface appears to be covered in parallel grooves. Experiments have shown that anchoring center initiation drives cerebellar foliation. However, the mechanism guiding the location of these anchoring centers, and subsequently cerebellar morphology, remains poorly understood. In particular, there is no definitive mechanistic explanation for the preferential emergence of parallel folds instead of an irregular folding pattern like in the cerebral cortex. Here we use mechanical modeling on the cellular and tissue scales to show that the oriented granule cell division observed in the experimental setting leads to the characteristic parallel folding pattern of the cerebellum. Specifically, we propose an agent-based model of cell clones, a strategy for propagating information from our in silico cell clones to the tissue scale, and an analytical solution backed by numerical results to understand how differential growth between the cerebellar layers drives geometric instability in three dimensional space on the tissue scale. This proposed mechanical model provides further insight into the process of anchoring center initiation and establishes a framework for future multiscale mechanical analysis of developing organs.
Androgen Suppression Therapy Is Associated with Lower Recurrence of Non-muscle-invasive Bladder Cancer.

Abstract Background The challenge of managing non–muscle-invasive bladder cancer (NMIBC) is its high recurrence rate. Clinical investigations have begun to explore the role of androgen suppression as an adjunct to bladder cancer (BC) treatment. Objective To examine the effect of androgen suppression therapy (AST) on recurrence and progression rate of risk-stratified NMIBC. Design, setting, and participants Male patients with NMIBC were identified retrospectively from a US institutional database between 2001 and 2017. AST included 5α-reductase inhibitor, gonadotropin-releasing hormone agonist, and antiandrogen. Patients who were exposed to AST prior to documented recurrence/progression were included in the treatment arm. BC was risk stratified to investigate the differential response to AST. Outcome measurements and statistical analysis Hazard ratios (HRs) for NMIBC recurrence and progression were estimated using Cox proportional hazards multivariate regression models with stepwise method. Recurrence-free survival (RFS) and progression-free survival (PFS) were compared between groups with and without AST. Results and limitations We identified a total of 274 males with a median follow-up period of 3.1 yr (interquartile range [IQR] 1.5–5.2). Thirty-six patients were exposed to AST with a median duration of 1.7 yr (IQR 0.7–2.6). AST was associated with a lower risk of recurrence (HR 0.53, 95% confidence interval 0.30–0.88) as well as improved RFS (p = 0.014). However, no significant reduction of progression or improvement of PFS (p = 0.23) was found with AST. After risk stratification, all five patients who progressed in the AST cohort had high-risk disease on initial transurethral resection (TUR), whereas no patients with low/intermediate-risk disease progressed on AST. Limitations of the study include nonstandardized initiation of AST in relation to initial TUR, lack of androgen level quantification, and small sample size in the treatment arm. Conclusions In this retrospective, single-institution study, AST was associated with a lower risk of recurrence in NMIBC. No significant association between AST and progression was found. Further investigation is warranted to define the role of AST as an adjunctive therapy for NMIBC. Patient summary Non–muscle-invasive bladder cancer is a highly recurrent disease that often requires patients to undergo repeated surgical treatments. This single-institution report suggests that medical suppression of androgen may be a potential preventive therapy to reduce recurrence in certain patients.
Effects of e-Beam Parameters on Sub-micron Ferroelectric Domain Engineering in Liquid Phase Epitaxy LiNbO3 by Direct - Write e – Beam

By using the direct-write e-beam technique with liquid phase epitaxy LiNbO3 thin films, we have successfully produced sub-micron domain structures for achieving dynamically switchable filters in a periodically poled lithium niobate (PPLN) waveguide. The effects of direct-write e - beam parameters are investigated to achieve sub-micron periodic domain structures in homoepitaxial liquid phase epitaxy (LPE) LiNbO3 thin films. More regular structures appear at acceleration voltages higher than 20 kV and areal dose range 350 μC / cm2 ~ 450 μC / cm2 with lower scanning speeds. Under these optimal conditions, an approximately 500 μm-long grating of a 1.1 μm period, consisting ~ 180 nm domains is achieved.
Landscape Patterns Associated with Occupancy of Disturbance-Dependent Birds in the Blackland Prairie Ecoregion of Alabama and Mississippi

The Blackland Prairie Ecoregion of Alabama and Mississippi, formerly a mosaic of prairie, shrubland, and forest, has undergone massive landcover change in the past 2 centuries. Even though the region is now dominated by agriculture and ranchland, disturbance-dependent birds—a guild in decline—continue to inhabit the Blackland Prairie Ecoregion. Therefore, we investigated the relationship between landscape patterns at 4 spatial scales (within 200 m, 600 m, 1000 m, and 3000 m of survey points) and occupancy for 17 species of disturbance-dependent birds. We used a Bayesian occupancy model to relate avian detections to landcover covariates and used stochastic search variable selection to identify covariates that were relevant to occupancy for each species. The amount of canopy cover was the covariate most frequently identified as relevant to occupancy. Grassland and open-country species showed a negative relationship with canopy cover, while shrubland species showed a positive relationship with canopy cover. The association between occupancy and covariates was strongest at the smaller spatial scales, though covariates at the larger spatial scales were still selected as relevant to occupancy. Our results highlight the importance for land managers to consider the landscape context prior to making on-the-ground conservation action; measures aimed to conserve grasslands, for example, will likely be ineffective if they take place in landscapes with high canopy cover.
A diamond-plus principle consistent with AD

After showing that $$AD +DC $$ refutes $$\lozenge ^+_\kappa $$ for all regular cardinals $$\kappa \ge \omega _1$$ , we present a diamond-plus principle $$\lozenge _{{{\mathbb {R}}} }^+$$ concerning all subsets of $$\varTheta $$ . Using a forcing argument, we prove that $$\lozenge _{{{\mathbb {R}}} }^+$$ holds in Steel’s core model $${{{{\mathbf {K}}}({{{{\mathbb {R}}} }})}}$$ , an inner model in which the axiom of determinacy can hold. The combinatorial principle $$\lozenge _{{{\mathbb {R}}} }^+$$ is then extended, in $${{{{\mathbf {K}}}({{{{\mathbb {R}}} }})}}$$ , to successor cardinals $$\kappa >\varTheta $$ and to certain cardinals $$\kappa >\varTheta $$ that are not ineffable. Here $$\varTheta $$ is the supremum of the ordinals that are the surjective image of the set of reals $${{{\mathbb {R}}} }$$ .
Temporal changes in the corpus luteum during early pregnancy reveal regulation of pathways that enhance steroidogenesis and suppress luteolytic mechanisms

Although rescue of the corpus luteum (CL) is required for pregnancy, luteal function during maternal recognition of pregnancy remains largely unexplored. CL were collected from pregnant cattle on days 14, 17, 20, and 23, to encompass the maternal recognition of pregnancy period. Next-generation sequencing was used to profile mRNA abundance during this time, while tandem mass spectrometry and nanostring technology were used to profile proteins and miRNA, respectively. A total of 1157 mRNA were differentially abundant, while 27 miRNA changed, and 29 proteins tended to change. mRNA that increased were regulators of interferon signaling and DNA repair, while those that decreased were associated with luteolytic processes, such as calcium signaling and matrix metallopeptidase (MMP) signaling, indicating inhibition of these processes. One of these, MMP12, was regulated by prostaglandin F2A in vitro. mRNA that were maximally abundant on day 20 were primarily associated with immune processes. Two of these, C-C motif chemokine ligand 1 and NFKB inhibitor alpha, were regulated by interferon tau in vitro. MiRNA that increased were predicted to inhibit phosphatidylinositol signaling, while those that decreased may be negative regulators of steroidogenesis. One protein that was greater on day 20 than on day 14 was aldehyde dehydrogenase 1 family member A1 (ALDH1A1), which synthesizes retinoic acid. Pharmacological inhibition of this enzyme, or of retinoic acid receptor signaling, led to suppression of progesterone production in vitro. Overall, these data indicate that there are changes in the CL of pregnancy that are important for continued luteal function.
Review of Colander & Freedman’s Where Economics Went Wrong: Chicago’s Abandonment of Classical Liberalism

Colander and Freedman draw a much larger circle around recent criticisms of the economics discipline, arguing that the source of “where economics went wrong” lies in the discipline’s sublimation of the art of economic policy to its scientific counterpart. Whereas classical liberal blended the science of political economy with the art of policy-making, the methodological assumptions of 20th century economics, especially at Chicago, enshrined the “economist as policy scientist” as the new archetype of a modern policy advisor. The essay reviews their argument and examines four aspects of the history they tell that deserve greater attention than they provide.
Multiple Star Formation to the Bottom of the IMF

The frequency and properties of multiple star systems offer powerful tests of star formation models. Multiplicity surveys over the past decade have shown that binary properties vary strongly with mass, but the functional forms and the interplay between frequency and semimajor axis remain largely unconstrained. We present the results of a large-scale survey of multiplicity at the bottom of the IMF in several nearby young associations, encompassing 78 very low mass members observed with Keck laser guide star adaptive optics. Our survey confirms the overall trend observed in the field for lower-mass binary systems to be less frequent and more compact, including a null detection for any substellar binary systems with separations wider than ~7 AU. Combined with a Bayesian re-analysis of existing surveys, our results demonstrate that the binary frequency and binary separations decline smoothly between masses of 0.5 Msun and 0.02 Msun, though we can not distinguish the functional form of this decline due to a degeneracy between the total binary frequency and the mean binary separation. We also show that the mass ratio distribution becomes progressively more concentrated at q~1 for declining masses, though a small number of systems appear to have unusually wide separations and low mass ratios for their mass. Finally, we compare our results to synthetic binary populations generated by smoothed particle hydrodynamic simulations, noting the similarities and discussing possible explanations for the differences.
Abstract 027: Individual-level Fine Particulate Air Pollution Is Associated With Arrhythmia In Adolescents

Introduction: Fine particulate (PM2.5) exposure has been related to higher propensity of arrhythmias in adults. However, the association between PM2.5 exposure and arrhythmia in adolescents remains...
Dielectric behavior of graphite, with assimilation of the AC permittivity, DC polarization and DC electret

Abstract The dielectric behavior of polycrystalline graphite is addressed by assimilating the DC electric polarization, AC permittivity, DC electret behavior, and their grain-size dependence. The AC-permittivity-related polarization is weaker than the DC-electret-related polarization, involving fewer carriers, because the depolarization is slower than polarization. The DC-current-induced polarization is even weaker than the AC-permittivity-related polarization, involving even fewer carriers. A decrease in the grain size increases the fraction of carriers that participate in the DC-polarization/AC-permittivity/DC-electret through carrier-atom interaction at the grain boundaries, thereby increasing the permittivity and the electret's electric field. The electric field increases with increasing resistivity and increasing inter-electrode distance l. DC-polarization/DC-depolarization and electret discharge/charge are faster for a smaller grain size. Both electric field and the reciprocal of the capacitance increase linearly with l, suggesting a model of dipoles in series. The amount of charge at each end of the overall dipole is greater for a smaller grain size, while the discharge time per unit electret-participating charge is shorter. In spite of the decrease in the fraction of carriers that participate with increasing l, the electret energy density is much increased by increasing l, because it depends on the power density and discharge time, both of which increase with l.
The role of science policy in developing digital biomarkers

Computing and digital technology, have transformed many industries. While the transformations in health and medicine have been slow to be realized, the digitization of our lives has created opportunities to better monitor and assess health. Current work on digital biomarkers suggest they may offer a whole new window into understanding disease trajectories and treatment effects. While the opportunities in this area great, there remain challenges to realizing digital biomarkers for adoption in health. This talk will focus on some of the promise and challenges in the development of functional digital biomarkers. The talk will highlight the challenges of developing and validating markers within the constantly challenging digital landscape, as well as exploring the line between monitoring digital biomarkers and surveillance.
Gating mechanisms in hyperpolarization-activated cyclic nucleotide-gated ion channels

Hyperpolarization-activated cyclic nucleotide-gated 1on channels (HCN) are gated by voltage, that is, they are able to detect changes in voltage and convert that into work for opening and closing (gating) the channel gate. The focus of this thesis was to investigate the gating mechanisms in HCN channels. Results from these experiments revealed that HCN channels have a voltage sensor (S4) similar to K v channels but have reversed gating. This makes up the first half of the thesis. In addition, the outward currents through HCN channels are susceptible to a voltage-dependent block by intracellular Mg +. The experiments relating to the Mg+ block make up the second half of the thesis. HCN channels mediate an inward cation current that contributes to spontaneous rhythmic firing activity in the heart and brain. These channels share homology with depolarization-activated Kv channels, including six transmembrane domains (S 1-S6) and a positively charged S4 segment. The S4 domain has been shown to function as the voltage sensor and undergo a voltage-dependent movement in the Shaker K+ channel. Experiments making up the first half of the thesis, incorporated the substituted cysteine accessibility method in conjunction with two-electrode voltage clamp to test for state dependent movement in the S4 domain of HCNl. Six cysteine mutations (R247C, T249C, 1251C, S253C, L254C, and S261 C) were used to assess S4 movement of the heterologously expressed HCNl channel in Xenopus oocytes. State-dependent accessibility was found for four residues, T249C and S253C from the extracellular solution and
Inhibiting the Expression of a Classically Conditioned Behavior Prevents Its Extinction

The underlying neuronal substrates and behavioral properties that might mediate extinction of the classically conditioned eye-blink response (CR) were examined. Four groups of rabbits were trained to perform the CR. Two of the groups then received either three or six sessions of tone-alone extinction training while the motor nuclei that mediate expression of the CR (facial nucleus and accessory abducens) were reversibly inactivated with microinjections of the GABA agonist muscimol. After these inactivation extinction sessions, rabbits received four more extinction sessions without inactivation. Two groups of controls received either three or six extinction sessions while saline vehicle was infused into the motor nuclei, followed by four sessions with no infusions. Saline infusions had no effect on extinction, and controls extinguished the CR normally over the first three to four sessions. In contrast, muscimol inactivation of the motor nuclei completely prevented any performance of CRs during the three or six inactivation extinction sessions. At the start of the four extinction sessions without inactivation, rabbits performed CRs at the same rate and amplitude as controls on their first extinction sessions. The muscimol rabbits then extinguished the CR normally over the four sessions without inactivation. In short, inactivation of the motor nuclei completely prevented any extinction of the eye-blink CR with no effect on subsequent extinction without inactivation. These results are discussed in terms of possible neuroanatomical loci that might mediate the extinction process as well as how effects of manipulating CR performance during extinction may affect the extinction process.
Photodissociation Regions and Planetary Nebulae

FUV photons ( 103 yr), molecules will only survive inside dense clumps (>106 cm-3). H2 emission from such dense gas will show a thermal spectrum in the low v states. Finally, the physical conditions in the PDR associated with NGC 7027 are compared to those in other galactic and extragalactic PDRs
A Response to Desposato

We are grateful to Scott Desposato for his thoughtful review of The Handbook of National Legislatures and the comments he offers on the Parliamentary Powers Index (PPI), the tool that we developed to measure the strength of the national legislature for every country in the world. We agree with many of Desposato’s points, but would also like to respond to some of the criticisms. In his review, Desposato flags the mixing of formal and informal powers in the Legislative Powers Survey (LPS, on which the PPI is based). We also grappled with the distinction between de jure and de facto powers. Where the letter of the constitution and actual practice diverge, we coded the legislature’s de facto powers. Desposato notes that “mixing of formal and informal institutions closes a potentially interesting and important line of research on the interaction between formal and informal institutions.” We acknowledge that a study of de facto powers alone would have this shortcoming.Yet, by noting in the text where formal and informal powers diverge, we provide ample information for scholars who wish to investigate this matter. For example, in our answer to the question about whether the “legislature can conduct independent investigations of the chief executive” in Russia, we write, “No. Formally, the legislature can establish commissions to investigate the government. In practice, however, investigations are rare and subject to executive influence” (561). We take Desposato’s point that a divergence index, which registers the gap between actual and legal legislative powers, would be of great interest in its own right. We did not construct such an index, but our decision to present full information on every survey item for every country makes it possible for scholars interested in studying the discrepancy between de facto and de jure to pursue this line of investigation. Continuing with his critique of mingling formal and informal powers in the survey, Desposato argues that the relationship between the legislature’s strength and democracy may be partly endogenous because factors that make a country less democratic might also reduce Book Review 397
Fluorescence anisotropy (polarization): from drug screening to precision medicine.

Introduction: Fluorescence anisotropy (FA) is one of the major established methods accepted by industry and regulatory agencies for understanding the mechanisms of drug action and selecting drug candidates utilizing a high-throughput format.Areas covered: This review covers the basics of FA and complementary methods, such as fluorescence lifetime anisotropy and their roles in the drug discovery process. The authors highlight the factors affecting FA readouts, fluorophore selection and instrumentation. Furthermore, the authors describe the recent development of a successful, commercially valuable FA assay for long QT syndrome drug toxicity to illustrate the role that FA can play in the early stages of drug discovery.Expert opinion: Despite the success in drug discovery, the FA-based technique experiences competitive pressure from other homogeneous assays. That being said, FA is an established yet rapidly developing technique, recognized by academic institutions, the pharmaceutical industry and regulatory a...
Novel mechanism for UV sensitivity and apparent UV nonmutability of recA432 mutants: persistent LexA cleavage following SOS induction.

The recA432 mutant allele was isolated (T. Kato and Y. Shinoura, Mol. Gen. Genet. 156:121-131, 1977) by virtue of its defect in cellular mutagenesis (Mut-) and its hypersensitivity to damage by UV irradiation (UVs), which were phenotypes expected for a recA mutant. However, we found that in a different genetic background (lexA51 sulA211 uvrB+), recA432 mutants expressed certain mutant phenotypes but not the Mut- and UVs phenotypes (D.G. Ennis, N. Ossanna, and D.W. Mount, J. Bacteriol. 171:2533-2541, 1989). We present several lines of evidence that these differences resulted from the sulA genotype of the cell and that the apparent UVs and Mut- phenotypes of the sulA+ derivatives resulted from lethal filamentation of induced cells because of persistent derepression of sulA. First, transduction of sulA(Def) mutations into the recA432 strains restored cellular mutagenesis and resistance to UV. Second, recA432 sulA+ strains underwent filamentous death following SOS-inducing treatments. Third, cleavage of LexA repressor in a recA432 strain continued at a rapid rate long after UV induction, at a time when cleavage of the repressor in the recA+ parental strain had substantially declined. Fourth, we confirmed that a single mutation (recA432) conferring both the UVs and Mut- phenotypes mapped to the recA gene. These findings indicate that the RecA432 mutant protein is defective in making the transition back to the deactivated state following SOS induction; thus, the SOS-induced state of recA432 mutants is prolonged and can account for an excess of SulA protein, leading to filamentation. These results are discussed in the context of molecular models for RecA activation for LexA and UmuD cleavage and their roles in the control of mutagenesis and cell division in the SOS response. Images
Multiple cooperating mobile manipulators

The main goal of the paper is to present a framework and basic control algorithms for coordinating a small team of robots in tasks that involve grasping large objects and transporting them in a two-dimensional environment with obstacles. Each robot consists of a mobile platform and an arm. Some arms are passive while others are active. Our previous work (1998) addressed the manipulator design, the architecture, and the communication between robots. In this paper we address the control of the manipulators, the coordination between the platforms for a team of two or three cooperating robots, and the handling of flexible large objects.
A study of the effects of three commonly used software engineering strategies on software enhancement productivity

Abstract The results of a study of software enhancement projects involving identical information requirements are reported. A sample drawn from the 200 largest commercial banks in the United States was examined to determine the levels of programming, systems analysis, and project management effort necessary to implement interest reporting requirements of the U.S. Tax Equity and Fiscal Responsibility Act (TEFRA) of 1982. Results of the study indicate that firms using structured systems design and programming techniques expended twice as much effort to implement the TEFRA requirements as those using non-structured approaches. It was also found that firms purchasing software expended nearly the same amount of effort as those using traditional systems analysis and programming techniques.