cssi/SciSciGPT-SciSciNet huggingface dataset:
Solid-State Phase Relationships in the Calcia-Titania-Zirconia System at 1200°C

Phase relationships were investigated in the CaO–TiO2–ZrO2 system at 1200°C for compositions containing <50 mol% CaO using X-ray diffraction and electron probe microanalysis. The existence of two previously reported ternary phases, zirconolite (CaZrTi2O7) and calzirtite (Ca2Zr5Ti2O16), was confirmed. Each of these phases exhibited a significant range of homogeneity between TiO2 and ZrO2, while maintaining a nearly constant concentration of CaO. The ternary solubilities of the constituent binary phases were found to be small (typically <1 mol%), with the exceptions of the perovskites (CaTiO3 and CaZrO3). These latter phases displayed mutual solubilities of at least 22 mol% but exhibited significant variations in composition from grain to grain. Thermodynamic equilibrium was clearly not established in several samples, although most of the phase relationship information obtained was self-consistent.
Building learning: making a carbon neutral campus in McCall, Idaho

At the University of Idaho, an interdisciplinary group of faculty and students have created a design-build workshop sequence focused on the development of a carbon-neutral learning center at one of the university’s field campuses in McCall, Idaho. Located adjacent to Ponderosa State Park, an area populated by mature Ponderosa pine trees, the field campus is managed and directed by the McCall Outdoor Science School (MOSS), whose mission is to use the outdoors as a context to teach intermediate and high school students from the state of Idaho about science, place, and community. The new sustainable design curriculum, in the form of interdisciplinary workshops, aims to design and construct buildings at the field campus that will eventually embody the sustainable values taught by MOSS. The inaugural design workshop in the sequence began this semester with construction scheduled to begin in the summer of 2010. The intent of the design-build workshop sequence is to redesign and rebuild the field campus over a period of several years using carbon neutral design as an overriding goal. Passive design, in lieu of using heavily embedded technologies, will be a teaching focus in an effort to achieve the workshop and campus objectives. Because of the alpine forest campus location the workshop will have an additional focus on issues of fire-wise construction, snow management, and a use of underutilized materials in the built work. In addition to these aims, and in accord with the MOSS mission of using the outdoors as a teaching tool, the buildings themselves will act as ‘learning instruments’ for the young visitors, making explicit the sustainable principles embedded within. The eventual goal is that the entire campus will attain carbon-neutral performance and will set an example for future learning environments around the globe.
Tetramethyleneethanes: Non-Kekulé Ground State Triplets at Odds with Theory

The non-Kekule molecules trimethylenemethane 1 and tetramethyleneethane 2 have degenerate non-bonding molecular orbitals. Both molecules are expected to be ground state triplets in accord with Hund’s rule. The situation with respect to trimethylenemethane is settled; theory and experiment are in good agreement, it is a ground state triplet.1
The Strategic Case for Resource Nationalism

Governments have long been preoccupied with ownership of oil supplies as a means of increasing energy security. Debate about this practice has grown in recent years as Chinese national oil companies have increased their efforts to acquire overseas oil assets. While some “resource nationalists” praise this as a sound strategy, other scholars argue that countries are best served by relying on the free market for their oil imports.We make two arguments in this paper. First, the free market school is generally correct that in the conditions they examine (normal, functioning oil markets), strategies of resource nationalism confer little strategic gain (though more gain than those analysts acknowledge). But a strategy of resource nationalism can confer real strategic benefit during times of global supply shock, embargo, and blockade - times when price does not determine distribution of oil supplies.On China specifically, we offer a second set of arguments. (a) In the short term, China’s policies of resource nationalism cannot confer upon it true energy security as long as the United States can sever its transportation routes by force. China remains vulnerable to energy cutoffs in times of extreme crisis. (b) However, even in the short term, China’s strategy of resource nationalism pays off in various ways: it may win China better deals, and may secure supplies during oil shocks and embargoes. Furthermore, China’s policies of resource nationalism have raised the bar for others who would wield the oil weapon against it. (c) Finally, China’s resource nationalism strategy should be understood as part of a long-term effort. If its power continues to grow, China may someday field sufficient maritime power to protect its transport routes. China’s resource nationalism is laying the foundation today for a future in which it will be as energy secure as any of the major importers.
P64 – 2824: An atypical presentation of GABA antibody associated encephalitis

Introduction Anti-GABA receptor antibodies are characteristically associated with limbic encephalitis. We describe a unique presentation of encephalopathy and a movement disorder associated with these antibodies. Case A previously well two year old boy with normal development presented with a five day history of fever, lethargy and an increasingly unsteady gait. On presentation, he was found to have orofacial and focal left limb dystonia. Due to haemodynamic instability, he was intubated and ventilated. He was treated with intravenous antibiotics and aciclovir for presumed encephalitis. Brain CT and MRI were normal, and his CSF was acellular. Blood results revealed a normal CRP but raised ESR at 50. Initial autoantibody and vasculitis screening results were unremarkable. Antibodies against NMDA, VGKC and GAD were all negative. He was commenced on steroids and given a dose of intravenous immunoglobulin 4 days after his presentation. He thereafter started to make gradual recovery and was commenced on MMF. Extended autoantibody screening done during his initial presentation identified anti-GABA receptor antibodies. A year later, he continues to progress well apart from mild left-sided dystonia and has been weaned off immunosuppressants. Repeat testing at this stage demonstrated negative anti-GABA receptor antibodies. Discussion Multiple antibodies have been described in immune-mediated encephalitis as part of a rapidly expanding area of medicine. GABA receptors are inhibitory and antibodies against these usually produce symptoms of limbic encephalitis with prominent seizures. A paraneoplastic association is also described in adults with these antibodies, commonly related to small cell lung cancer. The clinical phenotype in childhood is rarely described. Immune therapy aids recovery in this condition, which is usually monophasic. Conclusion The presentation of encephalopathy and a movement disorder in the presence of normal brain imaging and CSF results suggests a possible immune-mediated process, and GABA antibody associated encephalitis should be considered.
Fetal Weight Estimation in Diabetic Pregnancies Using the Gestation-Adjusted Projection Method Comparison of Two Timing Strategies for Third-Trimester Sonography

OBJECTIVES The gestation-adjusted projection method extrapolates birth weight using third-trimester sonography. This technique is shown to be more accurate for sonographic examinations from 34 weeks to 36 weeks 6 days than 37 weeks to 38 weeks 6 days. Our objective was to determine whether even earlier sonographic examinations (31 weeks-33 weeks 6 days) further improves birth weight prediction in patients with diabetes. METHODS We conducted a retrospective cohort analysis of 388 pregnant women with pregestational or gestational diabetes who delivered at 37 weeks or later and had a sonographic examination performed between 31 weeks and 36 weeks 6 days. Sonographic examinations were categorized as "early" if performed at 31 weeks to 33 weeks 6 days or "late" if performed at 34 weeks to 36 weeks 6 days. We estimated birth weight using the gestation-adjusted projection method, compared errors in prediction of birth weight using the t test and Mann-Whitney U test, and performed a 2-sample test of proportions to compare prediction of macrosomia (birth weight >4000 g). RESULTS The early and late groups had similar mean gestational ages at birth (38 weeks 4 days versus 38 weeks 5 days; P = .13) and rates of macrosomia (10.7% versus 12.4%; P = .63). The early group had a greater mean absolute error (336 versus 297 g; P = .03) and percent error (9.9% versus 7.9%; P = .01) in birth weight prediction but a lower mean birth weight (3303 versus 3426 g; P = .02). Sensitivity for prediction of macrosomia was 19% in the early group versus 45% in the late group (P = .07), whereas specificity was similar (98% versus 96%; P = .27). CONCLUSIONS Using the gestation-adjusted projection method in our patients with diabetes, we found that sonographic examinations performed at 34 weeks to 36 weeks 6 days better predicted birth weight than those performed at 31 weeks to 33 weeks 6 days.
Generalizations of the Kodaira Vanishing Theorem

In this chapter, we give some striking generalizations of the Kodaira Vanishing Theorem with an arithmetical flavor due to Ramanujam [1],[2], Kawamata [2], and Viehweg [1]. We also give some additional characterizations of ampleness and state some vanishing theorems of Mumford [1] and Grauert-Riemenschneider [1] on singular spaces. We begin with the following generalization of Corollary (2.22) due to Ramanujam [1, Theorem 3].
Abstract 559: Machinery for Vitamin D Metabolism in Porcine Adipose--Derived Mesenchymal Stem Cells

Background: There is increasing evidence that vitamin D deficiency is an independent risk factor for cardiovascular disease. Cell-based therapy using adipose derived mesenchymal stem cells (MSCs) is an attractive option for endothelial layer regeneration post-angioplasty procedures. Vitamin D levels in circulating blood might regulate MSC based re-endothelialization of injured arteries. To our knowledge, the presence of vitamin D machinery in porcine MSCs is not yet reported. In this study, we investigated whether or not MSCs possess vitamin D machinery, including the expression levels of vitamin D receptor (VDR), vitamin D metabolizing enzymes (CYP24A1 and CYP27B1) after in vitro stimulation with active vitamin D, calcitriol. Methods and Results: MSCs isolated from porcine adipose tissue were characterized by positive staining for MSC markers CD44, CD73, CD90, and negative staining for macrophage marker CD11b and hematopoietic stem cell markers, CD34 and CD45; and by tri-lineage differentiation to osteoc...
Computer aided tissue engineering: application to biomimetic modeling and design of tissue scaffold

Computer-Aided Tissue Engineering (CATE) enables many novel approaches in modeling, design, and fabrication of complex tissue substitutes with enhanced functionality and improved cell-matrix interactions. Central to CATE is its bio-tissue informatics model that represents tissue biological, biomechanical, and biochemical information that serves as a central repository to interface design, simulation and tissue fabrication. This paper presents a study of applying CATE approach for the biomimetic design of bone tissue scaffold. A general CATE-based process for biomimetic modeling, anatomic reconstruction, CAD model based tissue scaffold design, quantitative computed tomography characterization, finite element analysis and freeform extruding deposition for fabrication of scaffold is presented.
A Problem of Governance: The Importance of Understanding Police Coordination

Early on it was argued that police sociology stood apart from much organizational sociology unnecessarily. While ihere are many things police sociology can learn from organizational sociology inter alia its adherence to reasonably transferable terminology and concepts, its general ideological neutrality regarding both methods and results, and its interest in communicating analogous findings across similar organizational forms — there are, conversely, lessons for organizational sociology to be found in police sociology.
Activity Pattern Discovery from Network Captures

Investigating insider threat cases is challenging because activities are conducted with legitimate access that makes distinguishing malicious activities from normal activities difficult. To assist with identifying non-normal activities, we propose using two types of pattern discovery to identify a person's behavioral patterns in network data. The behavioral patterns serve to deemphasize normal behavior so that insider threat investigations can focus attention on potentially more relevant. Results from a controlled experiment demonstrate the highlighting of a suspicious event through the reduction of events belonging to discovered patterns.
Progress in Bioengineered Whole Tooth Research: from Bench to Dental Patient Chair

Tooth loss is a significant health issue that affects the physiological and social aspects of everyday life. Missing teeth impair simple tasks of chewing and speaking, and can also contribute to reduced self-confidence. An emerging and exciting area of regenerative medicine based dental research focuses on the formation of bioengineered whole tooth replacement therapies that can provide both the function and sensory responsiveness of natural teeth. This area of research aims to enhance the quality of dental and oral health for those suffering from tooth loss. Current approaches use a combination of dental progenitor cells, scaffolds and growth factors to create biologically based replacement teeth to serve as improved alternatives to currently used artificial dental prosthetics. This article is an overview of current progress, challenges, and future clinical applications of bioengineered whole teeth.
AN EXPLORATORY STUDY FOCUSED ON MOVEMENTS AND INTERACTIONS IN THE WORK ENVIRONMENT

This study explores how the interior layout of the workspace can affect employees’ number of steps and face-to-face interactions. Eighteen participants were recruited for the study and the data was collected over ten business days. The participants completed self-report forms to report the number of steps and interactions they had daily. A positive relationship was found between distance and the number of steps and interactions. A negative correlation was found between depth, a construct of the space syntax theory, and the number of steps and interactions. The findings further examined whether the results support a social ecological model with the relationships between distance, depth, the number of steps and interaction, and moderate variables (personal, environmental, and organizational factors). Findings indicated that the number of steps, as a function of human behavior, was affected by distance and depth (as environmental factors), age and years of working (as personal factors), and work hours (as an organizational factor).
The Influence of Cultural Capital on How AmeriCorps Members Interpret Their Service

How do volunteers interpret what their service means to them? Is it based on the values the program instills, or on their experiences before volunteering? To answer these questions, I investigate service interpretation in the AmeriCorps program, a US-based social service agency. I conduct 22 in-depth interviews with AmeriCorps members to highlight how they use their cultural capital—rooted in their raised-class background—to interact differently with those they serve and to interpret different benefits of AmeriCorps. I find members from lower-income backgrounds use their past as a form of cultural capital to connect with their service population. On the other hand, members from more privileged backgrounds see the program as beneficial in the context of future work, yet have more difficulty connecting with those they serve. I conclude that the cultural capital learned from different social classes fosters different service interpretations for AmeriCorps members.
Cytomorphology of Fine Needle Aspiration of Thyroid

Thyroid nodules are common, up to 60 % of the general population may have sonographically detectable thyroid nodule(s) though only up to 5 % of these harbor malignancy. The challenge facing general physicians, endocrinologists, surgeons, and pathologists is to achieve an accurate preoperative diagnosis of malignancy in order to ensure appropriate treatment of the patients with thyroid nodules. FNA is the most commonly used modality that helps to establish a preoperative diagnosis of malignancy. Based on cytologic interpretation and regardless of the terminology employed, about 25 % of the thyroid nodules are classified as “indeterminate,” i.e., not possible to specify if the nodule is benign, malignant or suspicious for malignancy with a high risk of cancer. This chapter provides an overview of many aspects of thyroid FNA including commonly employed preparatory techniques, diagnostic classification, and cytomorphology along with histopathology of various thyroid lesions.
Peer Relationships Among Children With ASD: Interventions Targeting Social Acceptance, Friendships, and Peer Networks

Abstract Background: Developing meaningful friendships is an important protective factor for young children (Ladd, Kochenderfer, & Coleman, 1996; Rubin, LeMare, & Lollis, 1990) and is a skill with which children with autism spectrum disorder (ASD) often struggle (Chamberlain et al., 2007). Therefore, interventions targeting those skills play an important part in improving social outcomes. Aim: The purpose of this review is to describe and examine the effectiveness of intervention trials that have targeted the development of friendship, peer networks, and discrete social skills (e.g., engagement, social initiations) in young children with ASD. Method: Both single subject research designs (SSRDs) and randomized controlled trials (RCTs) examining interventions were evaluated for methodological quality ( Logan, Hickman, Harris, & Heriza, 2008 ; Higgins & Green, 2011 ). Data regarding participant and study characteristics (i.e., age, gender, measures, intervention setting, approach, and effect sizes) were extracted from all included studies. Results: 10 RCTs and 24 SSRDs with a combined sample size of 956 children were included. The majority of the interventions took place in children's schools and consistent effects were noted in increasing children's engagement with peers, especially when peer-mediated interventions (PMIs) were used. Less consistent effects were found for initiating, and responding to peers' social bids. Discussion: PMIs appear to be a promising intervention approach to help children with ASD to engage with peers. Targeted interventions in general saw larger effects than comprehensive intervention packages. There was also a trend towards the implementation of interventions in natural contexts such as schools and the use of community members as the agent of intervention, improving the generalizability of the interventions. Understanding which approaches and intervention components work for specific targets remains an important direction for future research, there is also a clear need to evaluate critical outcomes such as friendship development, as friendship was rarely explicitly measured.
A novel gene, cilia flagella associated protein 44, encoding an enzyme cleaving FtsZ and tubulin contributes to the regulation of secretory pathway.

We identified a novel gene, encoding the central region of the cilia and flagella associated protein 44 (Cfap44), that regulates trafficking of cellular components and morphology via the cleavage of cellular proteins (particularly β-tubulin). Although Cfap44 is registered in GenBank, the functions of both the central part and full-length protein are unknown except for a polymorphism associated with proprotein convertase 9 activity, the third gene of familiar hyper-cholesterolemia. In mice and humans, both unspliced and spliced RNAs were transcribed, and the spliced form was predominantly transcribed in the brain and embryonic tissues. In transfectants carrying this gene, various cellular processes such as cell division, transport of cellular components, and proteolytic processing of several proteins were found to be affected. The cleavage of β-tubulin was observed. A bacterial tubulin homolog, cell division protein FtsZ, was also cleaved in vivo and in vitro by the spliced form of Cfap44 product. Furthermore, the unspliced form showed proteolytic activity with low substrate specificity. Various biological activities of Cfap44 may be due to a direct effect of cleavage of β-tubulin inhibiting microtubule formation, or an indirect effect with the cross-recognition of the cleavage site between β-tubulin and other molecules.
Strengthening integration of clinical and public health systems to prevent maternal-child obesity in the First 1,000Days: A Collective Impact approach.

Abstract Introduction Obesity interventions may be most effective if they begin in the earliest stages of life, support changes across family, clinical, and public health systems, and address socio-contextual factors. Methods The First 1000 Days is a systematic program starting in early pregnancy lasting through the first 24 months of infancy to prevent obesity among low-income mother-infant pairs in three community health centers in Massachusetts. The program uses a Collective Impact approach to create the infrastructure for sustained, system-wide changes for obesity prevention across early life clinical and public health services, including Obstetrics, Pediatrics, Adult Medicine, Behavioral Health, Nutrition, Community Health, the Women, Infants and Children (WIC) program, and the Maternal, Infant and Childhood Home Visiting program. Program components include 1) staff and provider training; 2) enhanced gestational weight gain and infant overweight tracking; 3) universal screening of adverse health behaviors and socio-contextual factors; 4) universal patient navigation to support individual behavior change and social needs, while strengthening integration of clinical and public health services; 5) individualized health coaching for mother-infant pairs at high risk of obesity; and 6) educational materials to support behavior change. Results A quasi-experimental evaluation design will examine changes, between 2015 and 2019, in gestational weight gain and prevalence of infant overweight from 0 to 24 months of age. Conclusions The First 1000 Days program will examine the effectiveness of an early life obesity prevention program for mother-infant pairs. If successful, the program could provide a model for chronic disease prevention and health promotion among vulnerable families starting in early life.
Linear and Nonlinear Oscillators

The linear oscillator is a simple model that lies at the foundation of many physical phenomena and plays a crucial role in accelerator dynamics. Many systems can be viewed as an approximation to a set of independent linear oscillators. In this chapter, we will review the main properties of the linear oscillator including its response to resonant excitations, slowly varying forces, random kicks, and parametric variation of the frequency. We will discuss the impact of damping terms as well as how small, nonlinear terms in the oscillator equation modify the oscillator frequency and lead to nonlinear resonance.
You don't know me: Negative self-views interact with publicness and feedback to shape interpersonal impressions online

Abstract The present study extends identity shift and hyperpersonal literatures by examining how task feedback may affect interpersonal impressions depending on the publicness and valence of messages. In a 2 × 2 experimental design, participants engaged in an email discussion task with and without 38 CC-ed observers and received either positive or negative feedback. Contrary to expectations, the effects of feedback valence on perceived argument quality and incivility were intensified in the private rather than public condition. This effect was moderated by individuals’ self-views. Participants with high self-views responded critically to negative feedback, regardless of audience size. Those with low self-views responded more critically to private negative feedback than public negative feedback. Findings support a self-verification effect on identity shift, in that publicness activates the need for self-confirming feedback even when self-evaluations are negative. Findings stress the importance of studying individual differences in computer-mediated communication (CMC), particularly to understand the effects of audience in online impression formation.
Primary Biliary Cirrhosis: Clinical Aspects

Primary biliary cirrhosis, a chronic, progressive, and often fatal cholestatic liver disease, is characterized by the destruction of intrahepatic bile ducts, portal inflammation and scarring, and the eventual development of cirrhosis and liver failure. The diagnosis is usually made in a middle-aged woman (although the age range is 20–80 years) who initially has fatigue or itching or who is asymptomatic and has been found to have unexplained hepatomegaly or an elevated serum alkaline phosphatase level. Biochemical tests of liver function typically reveal a cholestatic pattern; i. e., the alkaline phosphatase and γ-glutamyltranspeptidase are disproportionately elevated compared with other biochemical tests. A positive antimitochondrial antibody test, present in 95% of patients with primary biliary cirrhosis, makes the diagnosis very likely. It is still important to ascertain that the bile ducts are patent. This can usually be done with ultrasonography or computed tomography (CT) scanning. If the results of these tests are equivocal, endoscopic retrograde cholangiopancreatography should be done. Percutaneous needle biopsy of the liver will provide confirmatory information and permit histologic staging of the disease. This is helpful in assessing prognosis.
Scaling Up Early Mathematics Interventions: Transitioning with Trajectories and Technologies

Transitions in the early years have substantial effects on children’s success in school. Moreover, lack of consideration of continuity and alignment may mislead both researchers and politicians to assume preschool effects ‘fade’, when it may be that poor transitions to primary school are to blame. We hypothesise that most present educational contexts are unintentionally and perversely aligned against early interventions. For example, primary curricula assume little mathematical competence, so only low-level skills are taught. Most teachers are required to follow such curricula rigidly and remain unaware that some of their students have already mastered the material they are about to ‘teach’. Teachers may be held accountable for getting the largest number of students to pass minimal competency assessments, engendering the belief that higher performing students are ‘doing fine’. In this way, we believe the present U.S. educational system unintentionally but insidiously re-opens the gap between students from low- and higher-resource communities. We conducted a large cluster randomised trial of an intervention that evaluated the persistence of effects of a research-based model for scaling up educational interventions, with one control and two intervention conditions. Only the intervention condition that included a follow-through treatment to support the transition to the primary grades maintained substantial gains of the pre-K mathematics curriculum.
Overview of Stochastic Scheduling Problems

No framework or classification scheme has ever been introduced for stochastic scheduling problems. It is more difficult to develop such a scheme for stochastic scheduling problems than for deterministic scheduling problems. In order to characterize a stochastic scheduling problem more information is required. For example, the distributions of the processing times have to be specified as well as the distributions of the due dates (which may be different). It has to be specified whether the processing times of the n jobs are independent or correlated (e.g., equal to the same random variable) and also which class of policies is considered. For these reasons no framework has been introduced in this book either
Gynecologic Oncology Group Study 229C: Personal Reflection

I heard the statistician say, “The drug does not have sufficient activity to study further in this population.” It was my co-investigator on GOG study 229C, Gefitinib in the Treatment of Advanced and Recurrent Endometrial Cancer (see related extended abstract in this issue*), calling from Roswell Park in Buffalo. He had just completed the analysis of data from 26 women treated on our study – a study which had been five years in the making from concept to clinical trial.
The British anti-psychiatrists: from institutional psychiatry to the counter-culture, 1960-1971

Almost 50 years after his death, R. D. Laing, once the counterculture’s favorite psychiatrist, and, indeed, for a while the best-known psychiatrist in the world, is once again the subject of intere...
Limitations of the Study and Future Research

Patnaik dwells into the unavoidable limitations of his research and the efforts undertaken to mitigate them. He acknowledges the lack of independent documentary evidence to corroborate the various stages of convening process even though care was taken to authenticate the champions’ account with other villagers, and by triangulation. Patnaik further points that he took care of the researcher bias as a government policy maker to a large extent with the help of audio-video recordings of the interviews and help of independent experts. He also allays apprehensions of external factors or interventions as having played a role in bettering social development indicators by arguing that such factors would only have hastened the change process and in no way diluted the need for it, or the process of convening apply to the historical accounts of their actions recounted by the various actors involved in the successful change process in the four cases discussed in the study. However, interpretive research is at the forefront of research methodology in most advanced research centres around the globe and given the Indian context, it is felt to be most apt as a methodology to draw reliable and valid conclusions. The limitations have been substantially mitigated by appropriate triangulation methods as discussed in Chapter 4. It is suggested that future research on this theme should take into account gender asymmetry as well as study of moderating factors such as size and heterogeneity on the institutional convening process.
Sympatho-Excitation in Heart Failure: Contribution of Skeletal Muscle Reflexes and the Protective Role of Exercise Training. Contribution of Skeletal Muscle Reflexes and the Protective Role of Exercise Training.

Abstract Skeletal muscle dysfunction in chronic heart failure (CHF) contributes to exercise intolerance and activation of the sympathetic nervous system. Exercise training has been advocated for patients with CHF and has been shown to improve quality of life and longevity. While enhanced protein degradation and oxidative stress contributes to this dysfunction exercise training of patients with CHF can reverse many of these abnormalities. The so-called “Exercise Pressor Reflex” (EPR) contributes to enhanced sympatho-excitation in CHF. This chapter discusses the mechanisms that contribute to increased sensitivity of the EPR and its reduction following exercise training. In this chapter, we provide the experimental evidence that group III skeletal muscle afferent neurons are primarily responsible for this sensitization. This sensitization may be due to enhanced purinergic signaling and increased oxidative stress. Importantly, exercise training reduces the EPR sensitivity, in part, by upregulation of the Transient Receptor Potential Vanilloid 1 receptor (TRPV1) and downregulation of P2X3 receptors in skeletal muscle of animals with CHF.
Treatment and dose prioritization in early phase platform trials of targeted cancer therapies

With the advances in the discovery of molecular targets, there is increasing interest in evaluating targeted therapies for disease subtypes characterized by certain biomarkers. Patients with a certain biomarker could potentially benefit from different experimental drugs, and, therefore, evaluating the relative efficacy of these drugs is an important objective. We consider the design of an early phase platform trial where multiple therapies are evaluated in patients with different biomarkers, with the objective of identifing the best drug at an efficacious and safe dose for a given disease subtype. We use the continual reassessment method to estimate the maximum tolerated dose of a drug and adopt hierarchical Bayesian modelling to estimate the efficacy of a drug administered at multiple doses. Using the continual reassessment method and hierarchical Bayesian modelling as the basis of inference, we propose various algorithms that prescribe the drug–dose for the patients using adaptive randomization. We demonstrate that adaptive randomization puts more patients at the right drug and dose on average than does balanced randomization, with slightly larger variability in distribution, and has no effect on the accuracy of drug–dose selection. Moreover the simulations show advantages of hierarchical Bayesian modelling over the beta–binomial model in scenarios with relatively flat or partially flat dose–efficacy relationships.
Why the Balkans

After trying to ignore the Balkans after the Cold War, the United States led NATO military interventions there at the height of the unipolar moment in 1995 (Bosnia) and 1999 (Kosovo) to stop wars that Washington feared would taint the post-Cold War world. Those interventions and a diplomatic one in Macedonia in 2001 were relatively successful, because they included serious international guarantees as well as major, multilateral, postwar peace- and state-building undertaken jointly by the United States and Europe with the consent of the warring parties. That experience suggests what will be necessary to deal with ongoing conflicts in Ukraine and the Middle East, though the multiplicity of players will make the latter far more difficult than the former.
Analytic Study of the Tadoma Method

Although results obtained with the Tadoma method of speechreading have set a new standard for tactual speech communication, they are nevertheless inferior to those obtained in the normal auditory d...
Pragmatic Pediatric Trial of Balanced Versus Normal Saline Fluid in Sepsis: The PRoMPT BOLUS Randomized Controlled Trial Pilot Feasibility Study.

BACKGROUND Resuscitation with crystalloid fluid is a cornerstone of pediatric septic shock treatment. However, the optimal type of crystalloid fluid is unknown. We aimed to determine the feasibility of conducting a pragmatic randomized trial to compare balanced (lactated Ringer's [LR]) with 0.9% normal saline (NS) fluid resuscitation in children with suspected septic shock. METHODS Open-label pragmatic randomized controlled trial at a single academic children's hospital from January to August 2018. Eligible patients were >6 months to <18 years old who were treated in the emergency department for suspected septic shock, operationalized as blood culture, parenteral antibiotics, and fluid resuscitation for abnormal perfusion. Screening, enrollment, and randomization were carried out by the clinical team as part of routine care. Patients were randomized to receive either LR or NS for up to 48 hours following randomization. Other than fluid type, all treatment decisions were at the clinical team's discretion. Feasibility outcomes included proportion of eligible patients enrolled, acceptability of enrollment via the U.S. federal exception from informed consent (EFIC) regulations, and adherence to randomized study fluid administration. RESULTS Of 59 eligible patients, 50 (85%) were enrolled and randomized. Twenty-four were randomized to LR and 26 to NS. Only one (2%) of 44 patients enrolled using EFIC withdrew before study completion. Total median (interquartile range [IQR]) crystalloid fluid volume received during the intervention window was 107 (60 to 155) mL/kg and 98 (63 to 128) mL/kg in the LR and NS arms, respectively (p = 0.50). Patients randomized to LR received a median (IQR) of only 20% (13 to 32) of all study fluid as NS compared to 99% (64% to 100%) of study fluid as NS in the NS arm (absolute difference = 79%, 95% CI = 48% to 85%). CONCLUSIONS A pragmatic study design proved feasible to study comparative effectiveness of LR versus NS fluid resuscitation for pediatric septic shock.
Knowledge, attitude and practice (KAP) of foodborne parasitic diseases among middle school students in Xuzhou City.

OBJECTIVE To investigate the status of knowledge, attitude and practice (KAP) of foodborne parasitic diseases among middle school students in Xuzhou City, so as to provide a reference to the health education. METHODS A total of four middle schools were selected and their students were investigated with the basic information questionnaire and questions of foodborne parasitic diseases. RESULTS The awareness rates of parasitic diseases, hazards and transmission were 56.50%, 66.33% and 70.50% respectively. The awareness rates of transmission of the diseases in the senior high school students and urban students were higher than those in the junior middle school students and rural students (χ2 = 8.684, 8.470, both P < 0.05). The formation rates of not drinking raw water and not eating raw food were higher among the female students than those among the male students (χ2 = 7.675, 15.230, both P < 0.05). The formation rate of not eating raw food was higher among the senior high school students than that among the junior middle school students (χ2 = 49.276, P < 0.001), and the formation rates of washing hands before meals and not keeping pets were higher among the urban students than those among the rural students (χ2 = 5.833, 13.443, both P < 0.05). Totally 64.83% of the students would not eat food that might be infected with foodborne parasites, and the proportion of girls was higher than that of the boys (χ2 = 11.690, P < 0.05), and 20.5% of the students would suggest others not eating food that might be infected with foodborne parasites, and 81% of the students would plan to get rid of bad habits. CONCLUSIONS The cognition of foodborne parasitic diseases is poor among the middle school students in Xuzhou City. The health education work on foodborne parasitic diseases should be strengthened.
Film, Art, and Pornography

This chapter rehearses the historical discourse over pornography with the intent of orienting the reader to the discourse and motivating a more constructive approach to dealing with pornography. Topics covered include pornography and obscenity law in the context of First Amendment protections to freedom of speech, pornography as harmful, including the arguments that pornography causes sexual violence or foments discrimination, the value of pornography, and whether pornography in general, and pornographic films in particular are art. The overall approach to this chapter is exploratory and the conclusions offered are tentative. The goal of this piece is simply to motivate a more robust understanding of pornography, its place in society, and its place in the artworld.
Abstract LB-C10: Preclinical synergistic anti-tumor effect against multiple cancer types by EZH2 inhibitor EPZ-6438 plus imipridone ONC201 to mimic H3K27M mutation observed in DIPG tumors that respond to ONC201 in the clinic

ONC201, the founding member of the imipridone class of small molecules, has broad spectrum anti-tumor activity and achieved tumor regressions and prolonged disease stability in clinical trials, especially in patients with histone H3 K27M mutated glioma. Levels of H3K27 dimethylation (H3K27me2) and trimethylation (H3K27me3) are reduced globally in H3 K27M patient samples. EZH2 is the catalytic component of the Polycomb Repressor Complex 2 (PRC2), a conserved multi-subunit that represses gene transcription by methylating lysine 27 on Histone H3 (H3K27). EZH2 is frequently overexpressed or mutated (activating) in numerous human malignancies and EZH2 inhibitors represent a promising therapeutic strategy. We hypothesized that cancer cells could be sensitized to ONC201 by EZH2 inhibition through suppression of H3K27 methylation that may mimic tumors such as DIPG with H3K27M mutations which are known to respond to ONC201 in the clinic and are defective in H3K27 methylation. We treated cancer cells from different tissue origins including breast cancer, pancreatic cancer, colorectal cancer, GBM, and DIPG with single agent ONC201, EZH2 inhibitor EPZ-6438 or the combination of ONC201 plus EPZ-6438. Cell viability was determined with the Cell Titer-Glo assay. Integrated stress response (ISR) activity widely observed in ONC201-treated tumor cells was evaluated using Western blot analysis of ATF4 and apoptosis by analysis of PARP cleavage. Our results demonstrate that ONC201 synergistically reduced cell viability, induced integrated stress response and apoptosis in combination with EZH2 inhibitor EPZ-6438. There was greater induction of ATF4 in combination therapy-treated tumor cells versus monotherapy. Intriguingly, U-251 GBM cells that were resistant to ONC201 under hypoxia could be sensitized to ONC201 by EZH2 inhibitor EPZ-6438. Our findings provide a preclinical rationale for developing ONC201 and EZH2 inhibitors as a novel synergistic combinatorial regimen with the potential for clinical translation in the treatment of several human malignancies including GBM, pancreatic cancer, colorectal cancer, and breast cancer. Citation Format: Yiqun Zhang, Lanlan Zhou, Shengliang Zhang, Robyn Borsuk, Howard P. Safran, Attila A. Seyhan, Wafik S. El-Deiry. Preclinical synergistic anti-tumor effect against multiple cancer types by EZH2 inhibitor EPZ-6438 plus imipridone ONC201 to mimic H3K27M mutation observed in DIPG tumors that respond to ONC201 in the clinic [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr LB-C10. doi:10.1158/1535-7163.TARG-19-LB-C10
Induction of IL-12 and IL-23 through toll-like receptors in dendritic cells differentially regulates the balance between chronic inflammation and anti-tumor immunity: implications for cancer vaccines and carcinogenesis

2473 Toll-like receptor (TLR) agonists critically regulate immune responses by virtue of specialized receptors in dendritic cells (DC). Besides induction of co-stimulatory molecule expression in DC, the ligation of TLRs triggers production of third signals, such as IL-12 and IL-23 that affect T cell polarization. Recent studies have suggested that IL-12 and IL-23 drive divergent signaling pathways. IL-12 induces Th1 CD4 T cells and CD8 T cells (Tc1) displaying high functional avidity, whereas IL-23 promotes both Th1 Tc1 memory but also and more critically Th17 development and chronic inflammation. The balance between IL-12 and IL-23 produced by DCs may influence the type of immune response they initiate and therefore affect the dynamic between tumor promotion and tumor immunity. In this study, we assessed the production of IL-12 and IL-23 by classical human monocyte -derived DCs treated with TLR agonists. DCs were stimulated with single TLR agonists (LPS or R848); dual TLR agonists (LPS and R848); or IFN-Γ and single TLR agonist. The surface phenotype, cytokine secretion profile and functional properties of these DCs were then compared. DCs in all groups demonstrated a mature phenotype after stimulation with TLR agonists. DC stimulated by LPS or R848 alone produced IL-23, but little or no IL-12, (Ratio of IL-12 to IL-23 is between 0.002-0.26, N=7). When treated with IFN-Γ and LPS or R848 and LPS (two TLR), DCs secreted large amounts of IL-12 and IL-23 (Ratio of IL-12 to IL-23 is between 0.2-1.2 N=7). In addition, the tumor associated inflammatory mediator prostaglandin E2 (PGE2) promoted IL-23 production while inhibiting IL-12 production. Corresponding to their cytokine secretion patterns, in a mixed lymphocyte reactions (MLR) or antigen specific sensitizations DCs activated by single TLR agonist LPS stimulated CD4 T cells toward Th17 cell differentiation, whereas DCs activated by IFN-Γ and LPS or dual TLR agonist activated DC polarized CD4 T cells towards a strong IFN-Γ producing Th1 response. Most strikingly, DCs activated by dual TLR agonists R848 and LPS or IFN-Γ and LPS generated high avidity CD8 T cells which recognized melanoma cell lines expressing endogenous tumor antigens, whereas DCs stimulated by LPS alone induced low avidity IL-17 secreting CD8 T cells. Our results demonstrate that DC activated by single TLR agonists secreted IL-23 with no or little IL-12, favoring a Th17 polarized inflammatory response. Dual TLR agonists (R848 and LPS) or IFN-ΓA\#381; and LPS generate DCs that produce IL-12 and IL-23, favoring anti-tumor immunity. These results have important implications for balancing chronic inflammation long known to promote tumor development against anti-tumor immunity and should be taken into account in the design of anti-cancer vaccines.
Broadband Parametric-Gain Optimization of Partially Deuterated KDP with Two-Wavelength Tuning Curves

We investigate the use of phase-matching parametric-gain curves at two wavelengths to determine the deuteration level of a partially deuterated KDP crystal and optimize its broadband performance for optical parametric chirped-pulse amplification.
Pulsed focused ultrasound enhances the therapeutic effect of mesenchymal stromal cell-derived extracellular vesicles in acute kidney injury

Acute kidney injury (AKI) is characterized by rapid failure of renal function and has no curative therapies. Mesenchymal stromal cell (MSC)-derived extracellular vesicles (EVs) are known to carry therapeutic factors, which have shown promise in regenerative medicine applications, including AKI. However, there remains an unmet need to optimize their therapeutic effect. One potential avenue of optimization lies in pulsed focused ultrasound (pFUS), where tissues-of-interest are treated with sound waves. pFUS has been shown to enhance MSC therapy via increased cell homing, but its effects on cell-free EV therapy remain largely unexplored. We combine pFUS pretreatment of the kidney with MSC-derived EV therapy in a mouse model of cisplatin-induced AKI. EVs significantly improved kidney function, reduced injury markers, mediated increased proliferation, and reduced inflammation and apoptosis. While pFUS did not enhance EV homing to the kidney, the combined treatment resulted in a superior therapeutic effect compared to either treatment alone. We identified several molecular mechanisms underlying this synergistic therapeutic effect, including upregulation of proliferative signaling (MAPK/ERK, PI3K/Akt) and regenerative pathways (eNOS, SIRT3), as well as suppression of inflammation. Taken together, pFUS may be a strategy for enhancing the therapeutic efficacy of MSC-derived EV treatment for the treatment of AKI.
Solid-Phase Optical Manipulation and Assembly of Colloidal Particles

Most optical tweezers and manipulation techniques are operated in liquid environments, where the undesired Brownian motion and capillary forces limit the working performance. Here, we develop an all-optical technique, termed optothermally-gated photon nudging, for the versatile manipulation of particles on solid substrates at nanoscale accuracy.