cssi/SciSciGPT-SciSciNet huggingface dataset:
Morphologic effects of contact lens wear on the corneal surface.

We used specular microscopy of the corneal epithelium to examine 29 eyes of 29 patients each wearing one of five different types of contact lenses. We compared these with 24 eyes of 24 age-matched control patients. We found patients with aphakic extended wear soft contact lenses had significantly larger cells (818 +/- 186 microns2) than all other groups; and they were significantly larger than their age-matched control group (573 +/- 174 microns2) (P less than .002). The epithelial cells of extended wear soft contact lens patients (609 +/- 97 microns2) and daily wear rigid gas permeable contact lens patients (613 +/- 103 microns2) were larger than their control group of normal young patients (513 +/- 53 microns2). The cells of daily wear soft contact lens patients (484 +/- 111 microns2) and hard contact lens patients (517 +/- 46 microns2), however, were not different from controls. This study demonstrates a statistically significant shift in mean cell area of corneal epithelial cells in patients wearing some types of contact lenses.
3,3′-Dinitro­bis­phenol A

The title compound [systematic name: 2,2′-dinitro-4,4′-(propane-2,2-di­yl)diphenol], C15H14N2O6, crystallizes with two mol­ecules in the asymmetric unit. Both have a trans conformation for their OH groups, and in each, the two aromatic rings are nearly orthogonal, with dihedral angles of 88.30 (3) and 89.62 (2)°. The nitro groups are nearly in the planes of their attached benzene rings, with C—C—N—O torsion angles in the range 1.21 (17)–4.06 (17)°, and they each accept an intra­molecular O—H⋯O hydrogen bond from their adjacent OH groups. One of the OH groups also forms a weak inter­molecular O—H⋯O hydrogen bond.
Black-White Differences in Religiosity: Item Analyses and A Formal Structural Test*

Data collected as part of the Middletown project in Muncie, Indiana, are used to test both structural and magnitude differences between black and white dimensions of religiosity. The analysis of Linear Structural Relationships (LISREL) handles a number of potential problems more adequately than the traditional factor analytic approach. Four dimensions are examined: personal religious behavior, belief orthodoxy, ritual involvement, and consequentiality. Though the latent dimensions appear for both blacks and whites, the dimensions are not orthogonal. Further-more, the dimensions are not interrelated the same way for whites as they are for blacks, and specific items do not relate to the latent dimensions the same way for the two groups. Though a great deal of similarity exists for black and white religiosity, the results suggest, paraphrasing Stark (1972), that "differences of kind in piety" exist between blacks and whites. These differences have important implications for the future study of religion.
Fractional-order Systems and the Internal Model Principle

We consider the fractional-integrator as a feedback design element. It is shown, in a simple setting, that the fractional integrator ensures zero steady-state tracking. This observation should be contrasted with the typical formulation of the internal model principle which requires a full integrator in the loop for such a purpose. The use of a fractional integrator allows increased stability margin, trading-off phase margin against the rate of convergence to steady-state. A similar rationale can be applied to tracking sinusoidal signals. Likewise, in this case, fractional poles on the imaginary axis suffice to achieve zero steady-state following and disturbance rejection. We establish the above observations for cases with simple dynamics and conjecture that they hold in general. We also explain and discuss basic implementations of a fractional integrating element.
A Microcomputer Literacy Training Model for School Administrators

AbstractMicrocomputer literacy training models are becoming increasingly important to school district computer literacy training efforts. This study identified the administrative microcomputer training needs, school administrators’ attitudes toward microcomputer use, barriers and facilitators influencing administrative use of microcomputers, organizational factors needed to support such a change, and training delivery preferences and learning styles. Based on the data, an administrative microcomputer literacy training paradigm was designed which included cognitive, proficiency, intrinsic, and extrinsic goals, a training format, and change strategies.
Observations of Mating Behaviour in the Honeybee

SUMMARYAn apparatus is described by which tethered virgin queens could be suspended for restricted flight at desired heights up to 11 m., enabling observations on mating. Drones were attracted in large numbers and seemed to show normal mating behaviour. Their flight near the queen is described in detail, and the methods by which they locate her. Drones, first attracted by the scent of queen sex attractants, approached from windward, flying typically in sparse swarms that assembled and hovered in conical formation below and behind the tethered queens. Drones were consistently observed to mount on top of the queen's abdomen, but successful mating followed rather rarely. Mating behaviour was very stereotyped; the drone clasped the queen's abdomen and everted the genitals into the sting chamber, which must be open. Paralysis of the drone accompanied the onset of genital eversion; this caused the drone to swing over backwards, attached by the genitals which everted more completely as the physical restraints in...
Video Games as Meaningful Entertainment Experiences

We conducted an experiment to examine individuals’ perceptions of enjoyable and meaningful video games and the game characteristics and dimensions of need satisfaction associated with enjoyment and appreciation. Participants (N 512) were randomly assigned to 1 of 2 groups that asked them to recall a game that they found either particularly fun or particularly meaningful, and to then rate their perceptions of the game that they recalled. Enjoyment was high for both groups, though appreciation was higher in the meaningful- than fun-game condition. Further, enjoyment was most strongly associated with gameplay characteristics and satisfaction of needs related to competency and autonomy, whereas appreciation was most strongly associated with story characteristics and satisfaction of needs related to insight and relatedness.
Volume expansion measurements in metallic liquids and their relation to fragility and glass forming ability: an energy landscape interpretation.

Recent studies of Cu-Zr glasses have reported a rapid variation in the amorphous phase density near the optimal glass forming compositions, supporting the belief that the densest liquids are also the best glass formers. Here, we show that the measured densities of the Cu-Zr liquids at higher temperatures are not peaked sharply near these compositions, but the volume expansivities are. Theoretical studies have shown that the expansivity correlates with fragility near ${T}_{g}$; the experimental results presented here show that at high temperature they become anticorrelated. From energy landscape arguments, this indicates the existence of a crossover temperature for the expansivity-fragility correlation that scales inversely with the liquid fragility. These results lead to an improved understanding of the high temperature properties of liquids that form glasses and suggest a new method for identifying the best glass forming compositions within an alloy system from the properties of the equilibrium liquids.
Three New Schleiermacher Letters Relating to His Würzburg Appointment of 1804

In a letter written on his thirty-fifth birthday, November 21, 1803, Schleiermacher called the year just past the unhappiest of his life.' This troubled year provides the background for three letters Schleiermacher wrote to the Wuirzburg theologian Heinrich Eberhard Gottlob Paulus in January, February, and May, 1804, which are published for the first time below. The first letter is Schleiermacher's reply to an invitation, transmitted by Paulus, for Schleiermacher to join the theological faculty of the University of Wiirzburg. The second relates to Schleiermacher's acceptance of this Bavarian appointment and to his plans to move there. The third explains the necessity Schleiermacher subsequently faced of breaking his Wuirzburg contract in order to obey King Friedrich Wilhelm III's command to remain in his Prussian fatherland.
Ultrafast charge separation and indirect exciton formation in a MoS2-MoSe2 van der Waals heterostructure

We observe subpicosecond charge separation and formation of indirect excitons a van der Waals heterostructure formed by molybdenum disulfide and molybdenum diselenide monolayers. The sample is fabricated by manually stacking monolayer MoS2 and MoSe2 flakes prepared by mechanical exfoliation. Photoluminescence measurements confirm the formation of an effective heterojunction. In the transient absorption measurements, an ultrafast laser pulse resonantly injects excitons in the MoSe2 layer of the heterostructure. Differential reflection of a probe pulse tuned to the MoS2 exciton resonance is immediately observed following the pump excitation. This proves ultrafast transfer of electrons from MoSe2 to MoS2 layers, despite the strong Coulomb attraction from the holes in the resonantly excited excitons. Conversely, when excitons are selectively injected in MoS2, holes transfer to MoSe2 on an ultrafast time scale, too, as observed by measuring the differential reflection of a probe tuned to the MoSe2 resonance. T...
Pore Structure of Low Porosity DSP Cement Pastes

The pore structure of low porosity cement pastes containing varying quantities of silica fume has been examined using mercury intrusion porosimetry (MIP) and nitrogen adsorption (NA) measurements. The water:solid ratio for all DSP pastes studied was 0.18. It was observed that, as for conventional pastes, removal of water by solvent replacement with methanol minimizes changes to the pore structure. Vacuum or oven drying severely reduces specific surface area and obscures important trends. It was found that capillary porosity in excess of 10 nm (100 A) is essentially absent and that the pore volume measured can be considered an intrinsic part of the binding phase. The influence of silica fume and curing times on pore structure has been measured and the implications of the data will be discussed. Comparisons will be made with conventional cement pastes.
The La protein counteracts cisplatin-induced cell death by stimulating protein synthesis of anti-apoptotic factor Bcl2

// Tilman Heise 1 , Venkatesh Kota 1 , Alexander Brock 1 , Amanda B. Morris 1 , Reycel M. Rodriguez 1 , Avery W. Zierk 1 , Philip H. Howe 1 , Gunhild Sommer 1 1 Medical University of South Carolina (MUSC), Department of Biochemistry & Molecular Biology, Charleston, SC 29425, USA Correspondence to: Gunhild Sommer, e-mail: sommerg@musc.edu Keywords: La/SSB, LARP3, RNA-binding protein, cisplatin, mRNA translation Received: November 13, 2015 Accepted: March 28, 2016 Published: April 18, 2016 ABSTRACT Up-regulation of anti-apoptotic factors is a critical mechanism of cancer cell resistance and often counteracts the success of chemotherapeutic treatment. Herein, we identified the cancer-associated RNA-binding protein La as novel factor contributing to cisplatin resistance. Our data demonstrate that depletion of the RNA-binding protein La in head and neck squamous cell carcinoma cells (HNSCC) increases the sensitivity toward cisplatin-induced cell death paralleled by reduced expression of the anti-apoptotic factor Bcl2. Furthermore, it is shown that transient expression of Bcl2 in La-depleted cells protects against cisplatin-induced cell death. By dissecting the underlying mechanism we report herein, that the La protein is required for Bcl2 protein synthesis in cisplatin-treated cells. The RNA chaperone La binds in close proximity to the authentic translation start site and unwinds a secondary structure embedding the authentic AUG. Altogether, our data support a novel model, whereby cancer-associated La protein contributes to cisplatin resistance by stimulating the translation of anti-apoptotic factor Bcl2 in HNSCC cells.
302 DUPLICATION 22Q11.2: CLINICALLY HETEROGENEOUS NEW SYNDROME OR GENETIC POLYMORPHISM?

Duplication of 22q11.2, the velocardiofacial syndrome (VCFS) region, has been described as the mechanism underlying a new condition associated with a spectrum of physical and developmental features. We are aware of 50 cases in the literature. Duplication at 22q11.2 is expected to occur at equal frequency as its deletion; however, the duplication syndrome has been diagnosed much less frequently than VCFS. This apparent underdetection may result from the clinical variability of the syndrome. In reported cases common features have included dysmorphic facies, cleft palate, congenital heart disease, poor postnatal growth, seizures, and mild to severe cognitive impairment. Significant interfamilial and intrafamilial variation has been described. In an effort to refine our understanding of duplication 22q11.2, we present six newly ascertained cases from four families, including two mother-daughter pairs. Our cases demonstrate many clinical features that have been associated with the syndrome. However, they also include several manifestations not previously described: hemihyperplasia, multiple hemangiomas, congenital hypothyroidism, infantile cholelithiasis, and radial aplasia. Notably, two of our cases are parents of affected children who carry duplication 22q11.2 without apparent clinical sequelae. Our observations expand the range of anomalies associated with duplication 22q11.2. The presence of unaffected parents in our families suggests a complicated mechanism inheritance for this syndrome. Alternatively, duplication 22q11.2 may represent a polymorphism that has incidentally been detected in patients with unrelated conditions. We expect that duplication 22q11.2 will be found with increasing frequency as the range of associated clinical manifestations is more widely recognized. Careful study of families carrying this duplication will be necessary to distinguish a new syndrome from a possible polymorphism.
46 ACUTE RESPIRATORY DISTRESS SYNDROME ALVEOLAR FLUID INDUCES MYOFIBROBLAST GENES BUT SUPPRESSES KERATINOCYTE GROWTH FACTOR IN NORMAL HUMAN LUNG FIBROBLASTS.

Rationale Alveolar repair is critical to ARDS outcome. Myofibroblast induction is integral to healing by facilitating wound apposition (α-smooth muscle actin (α-SMA), secreting matrix (collagens 1 and 3), cytokines (TGF-β1 and connective tissue growth factor [CTGF]), and epithelial mitogens (keratinocyte growth factor [KGF]). We hypothesized that bronchoalveolar lavage fluid (BALF) from ARDS patients would induce multiple features of myofibroblasts. Methods ARDS BALF was collected within 48 hours of intubation. Patients with cardiogenic pulmonary edema were included as negative controls. ARDS and control BALF were incubated with normal human lung fibroblasts for 24 hours, and α-SMA, collagens 1 and 3, CTGF, TGF-β1, and KGF mRNA was measured by real-time RT-PCR. Results Ten ARDS patients and five negative controls were enrolled. The average age for ARDS patients was 53 ± 16 years. The average PaO 2 / FiO 2 ratio, compliance, and APACHE 2 scores were 118 ± 70, 21 ± 10, and 28 ± 8, respectively. ARDS BALF induced 110% more α-SMA ( p p p = .11) and 52% more collagen 3 ( p = .08) than controls. In contrast, control BALF induced 70% more KGF ( p r = −.78, p p p = .33). Conclusion Early ALI/ARDS BALF has predominant profibrotic characteristics and suppresses epithelial mitogen induction.
Should coal tar products carry cancer warnings

This article addresses the controversy whether over-the-counter products that contain coal tar concentrations greater than 0.5% must carry cancer warnings. Evidence that topical coal tar is carcinogenic in laboratory animals and humans is reviewed. In addition, the potential risk of internal malignancies arising from the topical use of coal tar is discussed. The view is expressed that the California court decision that such products should carry cancer warnings is correct.
Evaluation and Enhancement of Calibration in the American College of Surgeons NSQIP Surgical Risk Calculator

Background The American College of Surgeon (ACS) NSQIP Surgical Risk Calculator has been widely adopted as a decision aid and informed consent tool by surgeons and patients. Previous evaluations showed excellent discrimination and combined discrimination and calibration, but model calibration alone, and potential benefits of recalibration, were not explored. Because lack of calibration can lead to systematic errors in assessing surgical risk, our objective was to assess calibration and determine whether spline-based adjustments could improve it. Study Design We evaluated Surgical Risk Calculator model calibration, as well as discrimination, for each of 11 outcomes modeled from nearly 3 million patients (2010 to 2014). Using independent random subsets of data, we evaluated model performance for the Development (60% of records), Validation (20%), and Test (20%) datasets, where prediction equations from the Development dataset were recalibrated using restricted cubic splines estimated from the Validation dataset. We also evaluated performance on data subsets composed of higher-risk operations. Results The nonrecalibrated Surgical Risk Calculator performed well, but there was a slight tendency for predicted risk to be overestimated for lowest- and highest-risk patients and underestimated for moderate-risk patients. After recalibration, this distortion was eliminated, and p values for miscalibration were most often nonsignificant. Calibration was also excellent for subsets of higher-risk operations, though observed calibration was reduced due to instability associated with smaller sample sizes. Conclusions Performance of NSQIP Surgical Risk Calculator models was shown to be excellent and improved with recalibration. Surgeons and patients can rely on the calculator to provide accurate estimates of surgical risk.
[Etiological and molecular-epidemiological analysis on enterovirus associated encephalitis in Zhejiang, 2008-2012].

Objective In order to investigate etiology and molecular-epidemiological characteristics of enterovirus associated encephalitis (EAE) in Zhejiang,2008-2012.Method Cerebrospinal fluid and stool specimens were collected from suspected EAE patients,who were admitted to our hospitals.RD and Hep-2 cell lines were used to isolate enterovirus (EV).Serotypes of these EV isolates were identified through neutralization test by using serotype specific anti-sera.VP 1 genes of these isolates were sequenced,compared and used for the construction of phylogenetic tree.Results 127 (20.6％) human enterovirus (HEV) strains were isolated from 616 samples,which were collected from 610 patients.Serotypes of these EV isolates,including 60 coxsackievirus (CV),and 67 Echovirus (E) appeared to be CVA9,CVB1,CVB3-5,E3,E4,E6,E9,El4,E25 and E30,respectively.Predominant EV serotypes on EAE from 2008 to 2012 were seen as CVB3,CVB5,E6,E30 and E30,respectively.The full length of VP1 genes from different EV isolates was between 834 and 918 nucleotides.The VP1 gene similarities between these isolates and the reference strains were from 76.7％ to 85.0％ (nucleotides level) and 91.1％ to 97.9％ (amino acids level).The VP1 genes from E6 serotype isolates appeared most diverged,reaching 20.4％ (nucleotides level) attd 4.8％ (amino acids level).Based on the generated phylogenetic tree,all the EV isolates were fallen on the same branch of HEV-B,and the isolates in the same serotype formed one sub-branch,suggesting there existed geographical and temporal effects.E6 isolates diverged into two branchlets.Conclusion EVs from HEV-B were the etiologic agents for EAE in Zhejiang province from 2008 to 2012.All these EV isolates showed 12 serotypes,with predominant isolates varied every year.E30 was determined as the most dominant serotype while serotype E6 diverged into two sub-genetypes. Key words: Enterovirus associated encephalitis; Etiological spectrum; VP1 gene
Brief paper: A multimodel approach to stochastic team problems

This paper develops decentralized team strategies for decision makers using different models of the same large-scale system. Multiparameter singular perturbations are employed to capture the multimodel nature of the fast dynamic subsystems interconnected through slow dynamic variables. The small parameters are appropriately scaled so that the variables in both time scales are well defined. The system considered is linear and the cost criterion is quadratic. First, a multimodel solution is obtained when the decision makers make different noisy linear observations of the random initial state only. Then the solution to this static team problem is utilized to obtain a multimodel solution to the dynamic team problem with sampled observations under the one-step-delay observation sharing pattern. In both cases, the well-posedness of the multimodel solution is demonstrated.
Successful conservative management of a rare complication of tracheostomy; extensive posterior tracheal false pouch

Abstract Introduction With the advent of improved neonatal and pediatric intensive care management, tracheostomy is increasingly performed in children requiring prolonged ventilation. Even though tracheostomy is generally a safe procedure, there remains mortality and morbidity associated with it. Objective We report a rare complication of a tracheostomy tube resulting in extensive erosion and posterior tracheal false pouch secondary to a large tracheostomy tube and high positive end expiratory pressure in a 12-month-old infant. This was managed successfully with conservative treatment. Results A former 34-week premature infant was transferred to our pediatrics intensive care unit (PICU) with recurrent episodes of cardiopulmonary arrests due to suspected severe tracheobronchomalacia. The patient has bronchopulomonary dysplasia, severe restrictive lung disease and thoracic insufficiency from skeletal dysplasia requiring tracheostomy tube (TT) at two-month-old and mechanical ventilation. The 3.5 NEO TT was gradually upsized to a 5. The PEEP setting at transfer was 18cmH2O. The direct laryngoscopy and bronchoscopy showed moderate tracheomalacia at the innominate artery with a false pouch in the posterior tracheal wall that was 1.1cm below the tracheostomy stoma. A multi-disciplinary discussion including otolaryngology, PICU, Pulmonary Medicine, and Pediatric Surgery decided on conservative management. The false pouch healed and she was transferred back to referring PICU after a 46-day. Conclusion Tracheal wall erosion resulting in a pouch formation is a rare complication, but it should be considered in patients with long term tracheostomy with difficulty ventilation and oxygenation with positional change. DLB is a useful tool in its diagnosis and conservative management can be successful.
Written justifications to multiple-choice concept questions during active learning in class

ABSTRACTIncreasingly, instructors of large, introductory STEM courses are having students actively engage during class by answering multiple-choice concept questions individually and in groups. This study investigates the use of a technology-based tool that allows students to answer such questions during class. The tool also allows the instructor to prompt students to provide written responses to justify the selection of the multiple-choice answer that they have chosen. We hypothesize that prompting students to explain and elaborate on their answer choices leads to greater focus and use of normative scientific reasoning processes, and will allow them to answer questions correctly more often. The study contains two parts. First, a crossover quasi-experimental design is employed to determine the influence of asking students to individually provide written explanations (treatment condition) of their answer choices to 39 concept questions as compared to students who do not. Second, we analyze a subset of the ...
Mechanisms Controlling Selective Death of Leukemia Stem Cells in Response to Parthenolide.

Studies have shown that human acute myelogenous leukemia (AML) originates from a rare population of leukemic stem cells (LSCs). LSCs are found in nearly all AML subtypes and are sufficient to initiate and maintain leukemic growth in both long-term cultures and NOD/SCID mice. Since conventional chemotherapy drugs typically target actively cycling leukemic blast cells, the quiescent LSC population is likely to be drug resistant. Recently, we have described agents that can selectively kill LSC while sparing normal hematopoietic stem cells (HSC), thus demonstrating that quiescent LSC can be effectively destroyed. In particular, the sesquiterpene lactone parthenolide (PTL) is active as a single agent and can induce robust LSC-specific apoptosis. Therefore, we sought to further elucidate the mechanisms that result in leukemia-specific death. To this end, we have shown that PTL inhibits NF- κB and activates p53 in AML cells. Moreover, we have found that AML cells are highly-oxidized relative to their normal less-oxidized counterparts as determined by dihydrofluorescein diacetate (H2DCF-DA) fluorescence. Although PTL treatment was found to increase the basal oxidative load of both normal and leukemic cells, these increases were ultimately associated with only leukemia-specific death. High levels of reactive oxygen species are associated with genotoxic stress. Therefore, we hypothesized that PTL-mediated increases of the oxidative load in AML cells would be sufficient to produce genotoxic stress in AML cells, but not normal cells. We thus examined pathways involved in sensing and responding to oxidative and genotoxic stress. These studies demonstrate that upon PTL treatment, AML cells phosphorylate p53 on serine 15, and increase transcription of several downstream p53 pro-apoptotic genes, including GADD45, Bax, and p21. In addition, we detected phosphorylation of ATM on serine 1981, γ-H2AX, and phosphorylation of Chk2 on threonine 68. Importantly, these events are not observed in normal hematopoietic cells treated with PTL. These findings suggest a DNA damage/repair response to PTL in AML cells, and that normal cells appear to be resistant to this mechanism. Collectively, these data indicate that oxidative stress and DNA damage pathways may be a central component of PTL-induced apoptosis. We propose a model whereby AML cells exist in a physiological state in which PTL is able to preferentially invoke genotoxic stress in AML. Based on empirical evidence, we suggest that AML LSC also exist in such a state, and that PTL mediated inhibition of NF- κB and induction of stress leads to selective apoptosis of malignant cells, sparing normal cell populations.
Focusing of high-wave-vector magnons

The focusing of spin waves in magnetic materials has a number of important advantages for directing energy and thus information. In contrast to earlier works, we theoretically calculate the focusing of short-wavelength spin waves. We show that strong focusing of large wave-vector spin waves naturally occurs about halfway out in the Brillouin zone with no need for a magnetocrystalline anisotropy, dipolar effects, or an external magnetic field. The fact that the wavelength is on the order of the lattice constant leads to a form of lattice-induced anisotropy in the wave propagation. We also explore the tunability that is achieved by the application of both an external field and a uniaxial anisotropy. In this case there is a rotation of the focusing pattern. The rotation angle can be changed by varying the field strength, demonstrating tunability.
FEMINIST SCIENCE AND CHACOAN ARCHAEOLOGY: REPLY TO WARE

Ware's comment misses the point of Heitman's (2016) article and further demonstrates the need for feminist science perspectives.
A place for teleology

The Anthropic Cosmological Principle. By John D. Barrow and Frank J. Tipler. Clarendon: 1986. Pp.706. 25, 29.95.
Global Responses: The Search for Cures in the Development of Pharmaceuticals

In this article, Professor Stuart Walker examines several challenges that will be faced by the global pharmaceutical industry in the near future. These involve the question of improving the overall quality of life and care for millions in an era of cost containment. In order to respond to the increasing demands for advances in medicine while simultaneously retaining an industrially strong, innovative, and resilient economy, responsibility for the necessary changes will need to be shared among governments, the pharmaceutical industry, and health care professionals. In particular, four challengesfaced by the global pharmaceutical industry and their responses to each are discussed. The first of these is the needfor the industry to secure sufficient revenue from marketedproducts, so that they may both remain profitable and be able to invest in research and development to facilitate the creation of new medicines. The second challenge arises out of that research and development and involves the production of innovative medicines for the treatment or prevention of diseases for which there is no adequate treatment. Once these new medicines are developed, the third challenge faced by the industry is to bring the new medicines to market in a more rapid and efficient manner. Achieving this third goal is closely intertwined with thefinal challenge: restructuring the regulation of medicines to ensure the rapid review of new drug applications to get these new medicines to market. Although much remains to be done in achieving these goals, Professor Walker notes that the global pharmaceutical industry is taking decisive steps to approach these challenges and his article operates as a framework for continued progression.
Impaired autophagy correlates with golden retriever muscular dystrophy phenotype.

Introduction Duchenne muscular dystrophy (DMD) and golden retriever muscular dystrophy (GRMD) are X-linked disorders caused by mutations in the DMD gene. Autophagy was recently identified as a secondary therapeutic target for DMD. We hypothesized that autophagy would be reduced in GRMD. Methods Autophagic gene and protein expression was assessed in normal and GRMD skeletal muscles and correlated with phenotypic biomarkers. Results Muscles were differentially affected. Autophagy gene levels were lower than normal in the GRMD cranial sartorius (CS) but similar in the vastus lateralis (VL). Protein markers of autophagic flux, LC3B-II and p62, were higher in both GRMD muscles, in keeping with impaired autophagy. Protein levels correlated with a more severe phenotype. Autophagic structures were found in necrotic, fast-twitch GRMD myofibers. Discussion Our data suggest that autophagy is impaired in certain GRMD muscles. Differential GRMD CS involvement emphasizes that therapeutic modulation of autophagy could require specific muscle targeting. Muscle Nerve 58: 418-426, 2018.
Depression and Gender Dysphoria

Transgender youth, as a whole, are resilient and healthy young people, though a substantial minority will be at risk of depression and suicide. This chapter reviews three cases of transgender youth, describing their and their families’ journeys to come to terms with their gender identities, including periods of depression and self-injury. Existing literature is also reviewed to elaborate the nature, extent, and causes of depression among transgender individuals. The therapeutic approach to transgender youth presenting with depression or self-injury is discussed, along with the importance of family support and intervention. The process of determining whether to immediately refer depressed transgender youth for affirming medical interventions is also discussed.
The prisoner’s dilemma: gaming risk in joint venture gas arrangements

This paper explores the concept of gaming risk in joint venture gas agreements. It uses examples from the Queensland coal seam gas to liquefied natural gas projects to explore the objectives and risks from the perspective of various joint venture players. It considers the relative positions of joint venture parties: operator/non-operator, differing upstream and downstream operators, project participant/gas customer and majority/minority stakeholder. It also focuses on key risks from the relative perspective of each participant and how the joint venture construct can be used to obtain an optimal outcome for all parties. Where residual risk remains, this paper discusses how it can be managed through effective governance and control frameworks. The concept of game theory is usually espoused as a theoretical example of the prisoner’s dilemma. In the dilemma, each suspect can avoid a jail term if they squeal on their accomplice and the other stays silent. If, however, both suspects remain silent they both serve a minimum sentence. Readers may also be familiar with the phrases ‘win-win’ and ‘suspending self-interest’. Game theory has many applications – from business strategy to politics to war simulations. It has even been used to analyse the Brexit outcome. The gas industry is no exception. We have seen a plethora of joint venture arrangements in the gas industry, attempting to achieve optimal decision making while addressing the differing appetites for the amount and type of risks of the joint venture parties.
Temporal Consistency of Integrity-Ensuring Computations and Applications to Embedded Systems Security

Assuring integrity of information (e.g., data and/or software) is usually accomplished by cryptographic means, such as hash functions or message authentication codes (MACs). Computing such integrity-ensuring functions can be time-consuming if the amount of input data is large and/or the computing platform is weak. At the same time, in real-time or safety-critical settings, it is often impractical or even undesirable to guarantee atomicity of computing a time-consuming integrity-ensuring function. Meanwhile, standard correctness and security definitions of such functions assume that input data (regardless of its size) remains consistent throughout computation. However, temporal consistency may be lost if another process interrupts execution of an integrity-ensuring function and modifies portions of input that either or both: (1) were already processed, or (2) were not processed yet. Lack of temporal consistency might yield an integrity result that is non-sensical or simply incorrect. Such subtleties and discrepancies between (implicit) assumptions in definitions and implementations can be a source of inconsistenceies, which might lead to vulnerabilities. In this paper, we systematically explore the notion of temporal consistency of cryptographic integrity-ensuring functions. We show that its lack in implementations of such functions can lead to inconsistent results and security violations in protocols and systems using them, e.g., remote attestation, remote updates and secure resets. We consider several mechanisms that guarantee temporal consistency of implementations of integrity-ensuring functions in embedded systems with a focus on remote attestation. We also assess performance of proposed mechanisms on two commodity hardware platforms: I.MX6-SabreLite and ODROID-XU4.
TRENDS: How Does Partisanship Influence Policy Diffusion?:

We explore the role of partisanship in policy diffusion. Previous studies suggest that partisanship may influence the willingness of public officials to learn from the experience of their peers. Of...
From Monkey Business to Monicagate: Hijinks on the High Seas, Whitewater, a Vast Right-Wing Conspiracy, and the Rise of Fox News

Gary Hart’s involvement with Donna Rice and his mishandling of the media firestorm following its revelation perhaps made it possible for Bill Clinton to get away with his bad behavior with respect to extramarital relations. Short summaries of the events surrounding Hart’s political demise and Clinton’s slide to impeachment help to identify these behaviors as scandals and make note of the many ways in which each contributed to our pop culture.
Insights into the histology of planarian flatworm Phagocata gracilis based on location specific, intact lipid information provided by GCIB-ToF-SIMS imaging

Planarian flatworms are known as the masters of regeneration, re-growing an entire organism from as little as 1/279th part of their body. While the proteomics of these processes has been studied extensively, the planarian lipodome remains relatively unknown. In this study we investigate the lipid profile of planarian tissue sections with imaging Time-of-Flight - Secondary-Ion-Mass-Spectrometry (ToF-SIMS). ToF-SIMS is a label-free technique capable of gathering intact, location specific lipid information on a cellular scale. Lipid identities are confirmed using LC-MS/MS. Our data shows that different organ structures within planarians have unique lipid profiles. The 22-carbon atom poly unsaturated fatty acids (PUFAs) which occur in unusually high amounts in planarians are found to be mainly located in the testes. Additionally, we observe that planarians contain various odd numbered fatty acid species, that are usually found in bacteria, localized in the reproductive and ectodermal structures of the planarian. An abundance of poorly understood ether fatty acids and ether lipids were found in unique areas in planarians as well as a new, yet unidentified class of potential lipids in planarian intestines. Identifying the location of these lipids in the planarian body provides insights into their bodily functions and, in combination with knowledge about their diet and their genome, enables drawing conclusions about planarian fatty acid processing.
On the relation between high-redshift starburst galaxies and damped Ly-alpha systems

Essentially all high-redshift galaxies show evidence for strong large-scale outflows that should have a profound effect on the structure and kinematics of both the galaxies themselves and their environment. The interstellar absorption spectra of both Lyman break galaxies (LBGs) and local starburst galaxies are remarkably similar to those of damped Ly-alpha (DLA) systems in QSO spectra. Their rest-frame UV spectra typically show broad, blueshifted Ly-alpha absorption accompanied by low-ionization metallic absorption lines with complex profiles. Hydrodynamical simulations of galactic winds suggest that the absorption arises in a collection of dense clouds entrained in the hot wind and/or in shells swept up by the outflow. It seems likely that outflows would also give rise to DLA absorption when seen in absorption against a background QSO. It is emphasized that some differences are expected between the properties of DLA systems in the emission weighted galaxy spectra, which always probe the centers of star formation, and those in random sight lines through the outflow. The observed LBGs alone can account for all DLA absorption at z ~ 3 if the cross section for DLA absorption is pi*r^2 with r = 19 h^{-1} kpc. If the cross section is smaller than this, then the fraction of DLA systems arising in outflows could still be significant if there are many wind-driving galaxies below the current detection limits. This is certainly possible since the z=3 luminosity function is still rising down to the detection limit of 0.1 L_star and observations and simulations of local dwarf galaxies indicate that many of these fainter galaxies drive winds as well.
Limitations to Power Conversion Efficiency of InP Based Uni-traveling-carrier Photodiodes Due to Space Charge Resistance

The limiting mechanism for power conversion efficiency of uni-traveling-carrier photodiodes (UTC-PDs) for generating microwave signals is discussed. Experimental results are shown for a waveguide UTC-PD with a bandwidth of 50 GHz. The space charge resistance of this device is extracted and shown to limit the maximum power conversion efficiency to around 4%.
The Frailty Risk Score predicts length of stay and need for rehospitalization after kidney transplantation in a retrospective cohort: a pilot study.

Frailty is a widely used measure in older patients as a predictor of poor outcomes after hospitalization and surgery. There is a growing body of data in kidney transplantation suggesting frailty can predict adverse outcomes. There is interest in using chart review measures of frailty and multimorbidity, as they may be equally predictive as physical measurement. This approach holds promise for patient evaluation, identifying candidates for prehabilitation, and targeting resources towards those anticipated to have an increased rate of clinical challenges after kidney transplantation. Frail patients who are often older may place a large resource and economic burden on transplant programs. We applied a previously published chart review–based approach in a retrospective, pilot study to calculate the Frailty Risk Score (FRS) utilizing a cohort of kidney transplant patients. We reviewed concurrent comorbidities using the Charlson comorbidity (CM) score to determine the feasibility and utility of applying this approach in transplant patients to predict post-transplant outcomes such as length of hospitalization and the need for rehospitalization. Sixty kidney transplant recipients were evaluated by chart review, 23 characterized as older (> = 60) and 37 younger (ages 30–59). Median FRS score was 3 (range 1–7). Higher FRS was significantly associated with increased patient age (high FRS 19% in younger patients, 43% in older patients). Increased CM score was also associated with increased patient age. Patients with a high FRS stayed in the hospital for an average of 8 days, compared with 5.7 days for a low FRS. Patients with high FRS were readmitted an average of 2.9 times compared with an average of 1.1 for those with a low FRS. FRS score remained significant for predicting outcomes after adjustment for patient age. Elevated FRS prior to transplantation was associated with increased hospital stay and the need for readmission in kidney transplant recipients. This analysis demonstrates the potential strength of chart review in evaluating frailty prior to transplantation, permitting risk stratification and targeting of resources for rehabilitation and close post-transplant monitoring. Frail patients may benefit from targeted “prehabilitation” to attenuate the associated adverse clinical outcomes.
Personal and Academic Writing: Revisiting the Debate

More than ten years have passed since the widely publicized debate about person- al and academic writing that played out in the 1990s between Peter Elbow and David Bartholo- mae. But the question of the relative merits of these two different types of writing for student writers continues to be an issue of concern for teachers of composition, especially teachers of basic writing. In this article, I take another look at this important question. Using the psycho- linguistic theories of Jerome Bruner and James Britton as the basis for analysis, I reconsider the Elbow-Bartholomae debate. Then, using data from a qualitative study of reflective journal writ- ing I conducted, I argue that all students—and especially basic writers—need to reflect on their reading using personal, expressive language in order to acquire genuine academic discourse.
Rethinking the Strategic Woman Candidate

The historic advances made by women in the 2018 election are oftentimes viewed as part of an inevitable consequence of broader secular trends such as women’s progress in pre-political careers, or an anomaly such as the “Year of the Woman.” Both accounts obscure women candidates’ agency and strategic decision-making. In this chapter, I test the salience of issues that advantage women among the public and enable women candidates to broaden their message to address traditionally male-advantaged issues, such as the economy and taxes. Overall, congressional candidates in 2018 emphasized issues that they are stereotyped as more competent by voters. However, the diversity of campaign messages developed by incumbent and non-incumbent women, and Democratic and Republican women, suggests that women candidates are strategically shaping their campaigns to maximize their perceived strengths and minimize their perceived weaknesses in their appeals to voters.
Carbon pricing and economic populism: the case of Ontario

Carbon pricing policies face growing threats from populist attacks citing increased costs for consumers. This paper explores the potential for different strategies to protect carbon pricing policie...
Neuronal differentiation strategies: Insights from single-cell sequencing and machine learning

Neuronal replacement therapies rely on the in vitro differentiation of specific cell types from embryonic or induced pluripotent stem cells, or on the direct reprogramming of differentiated adult cells via the expression of transcription factors or signaling molecules. The factors used to induce differentiation or reprogramming are often identified by informed guesses based on differential gene expression or known roles for these factors during development. Moreover, differentiation protocols usually result in partly differentiated cells or the production of a mix of cell types. In this Hypothesis article, we suggest that, to overcome these inefficiencies and improve neuronal differentiation protocols, we need to take into account the developmental history of the desired cell types. Specifically, we present a strategy that uses single-cell sequencing techniques combined with machine learning as a principled method to select a sequence of programming factors that are important not only in adult neurons but also during differentiation.
Geometry and Principal Ideals

We explore two questions about integral domains of the form Z [ d ] = { a + b d | a , b ∈ Z } , where d ≠ 1 is square-free, meaning not divisible by the square of a prime. 1. Is there a reasonable ...
Design of the Class-E Power Amplifier Considering the Temperature Effect of the Transistor On-Resistance for Sensor Applications

This brief presents the analysis and compensation technique for the class-E power amplifier (PA) considering the temperature effect of the non-zero transistor on-resistance for sensor network applications. It is shown theoretically and by simulation that the output power level and efficiency decrease with the increase of the transistor on-resistance. The transistor biasing condition for achieving near-zero temperature dependence is derived. With this, a dynamic biasing technique is proposed to stabilize the output power of the PA over a wide temperature range. A prototype class-E PA was designed and fabricated in a 0.18- $\mu \text{m}$ CMOS process. Operating at 477 MHz, the PA has 4 output stages and the measured maximum output variation is about ±0.3 dB from −40 °C to 85 °C. This measurement has a good agreement with the theoretical analysis and simulation.
Childhood adversity, suicidality, and non-suicidal self-injury among children and adolescents admitted to emergency departments

ABSTRACT Purpose This population-based study explored the associations between childhood adversity and admission to emergency departments (EDs) with non-suicidal self-injury (NSSI) and with a suicide attempt. Methods A nationally representative cross-sectional sample of 5–17-year-olds admitted to EDs (N = 143,113,677) from 2006 to 2015 was utilized to assess the associations between childhood adversities, NSSIs, and suicide attempts. Results ED admissions with NSSI and admissions with a suicide attempt were associated with greater odds of exposure to individual childhood adversities (aORs: 1.34 to 5.86; aORs: 2.37 to 15.69, respectively). ED admissions with a suicide attempt were associated with greater odds of exposure to childhood adversities that might be perceived as less extreme or harmful (separation or divorce aOR: 15.69) than other adversities (death of a family member aOR: 13.38; history of physical abuse aOR: 9.56) as well as greater odds of exposure to three or more childhood adversities (aOR: 20.98). Conclusion Early detection of childhood adversities is important for identifying potential risk factors for self-harm. ED admission data can provide population-level surveillance to aid in these efforts and lead to more targeted and effective interventions aimed at reducing the negative effects of toxic stress that can result from exposure to childhood adversities.