cssi/SciSciGPT-SciSciNet huggingface dataset:
Homeostatic Control of Concentrations of Indole-3-Acetic Acid

Improved analytical techniques permit a reexamination of the early experiments of Skoog, van Overbeek, Went, Thimann, Haagen-Smit and Bonner (cf. 45). This reexamination demonstrates the importance of the ester and amide conjugates of indole-3-acetic acid (IAA), the “bound auxins”. Conjugates of IAA have been shown to have four metabolic roles: (1) IAA conjugates, and not tryptophan, are sources of IAA for the seed during germination (11); (2) an IAA conjugate is the “seed auxin precursor” (11,31); (3) conjugation of IAA protects it against peroxidative attack (8); and (4) reversible synthesis and hydrolysis of IAA conjugates provides a hormonal homeostatic system that is responsive to environmental controls (5). These roles have been adduced from studies of seedlings of Zea mays and their general applicability has not been established. However, we predict, in a process so basic as hormonal metabolism, that a modified interpretation of the biblical enunciation of comparative biochemistry, “all flesh is grass” (20), will be applicable.
AB023. Problem in the prevention and control of thalassaemia in Asia

Thalassaemia is the most common inherited single gene condition in the world. It is especially highly prevalent in the Asian Pacific region and poses a major public health problem. Carrier frequencies of the 2 major types of thalassaemia, the α and the β-thalassaemia, range from 3-40%, and vary from one country to another and within the same country in different ethnic groups. The most severe form of α-thalassaemia is Bart’s hydrops fetalis. This is a lethal condition that also poses an increased risk for maternal morbidity. Children with β-thalassaemia major are born healthy but require life-long transfusion with expensive iron chelation therapy, or bone marrow transplant to survive. Control of thalassaemia is further complicated by the prevalence of HbE in this region. Individuals who co-inherit HbE and β-thalassaemia have thalassaemia intermedia with severity range from mild to severe anaemia requiring transfusion. The key to control thalassaemia is to identify the population at risk and to offer genetic counselling and providing options to prevent the disease in the family. Routine full blood count and Hb electrophoresis can reliably identify most if not all β-thalassaemia and HbE carriers, and majority of α-thalassaemia carriers. Detection of mutation causing thalassaemia enables accurate identification of carrier at risk and allows early prenatal diagnosis to be carried out. This is especially important in identifying at risk individuals who are both α and β-thalassaemia carriers. However, molecular diagnosis is expensive and effective screening requires prior knowledge of the spectrum of mutations in the population. Planning of an effective screening strategy depends on available resources and prevalence of the disease. In many countries, screening is carried out at pregnancy when option for prevention is possible. While screening and prevention may be effective to reduce number of major type of thalassaemia, more resources for optimal treatment can then be made available to those who are seriously affected by the disease.
Current and Emerging Treatments for Psoriatic Arthritis

Psoriatic arthritis (PsA) is an immunologically mediated inflammatory disease characterized by arthritis, enthesitis, dactylitis, spondylitis, and psoriasis. Prior to the introduction of targeted biologic and synthetic medications, such as TNF inhibitors, the ability to pharmacologically control disease activity was limited, with only modest effects noted with Conventional oral (rather than traditional) oral medications such as methotrexate and sulfasalazine. The introduction of TNF inhibitors and subsequently other immunologically targeted therapies has substantially changed our ability to achieve significant response in all relevant clinical domains including the ability to inhibit progressive structural damage of joints. As understanding of the pathophysiology of psoriasis and PsA has deepened, so has our understanding of potential cellular signaling pathway inhibition which can downregulate pro-inflammatory cell and cytokine function. Since it is possible that different disease mechanisms play different roles in various tissue domains that are anatomically distinct, such as the joint, enthesia, spine, bone, and skin, it is important to be able to assess these domains separately using not only physical examination, but also advanced imaging and, at least in select studies, tissue immunohistology in order to document impact on these different domains. This chapter reviews the evidence for current and emerging therapies in all clinical domains of PsA.
Comparing Accuracy of Descriptive Assessment Methods Following a Group Training and Feedback

As one component of a functional behavioral assessment, descriptive assessments (DA) can help determine the maintaining variable of a student’s problem behavior in school. School districts often employ board-certified behavior analysts as consultants to conduct DAs by observing a student and recording the environmental variables surrounding problem behavior. However, consultants may have to rely on school personnel to conduct DAs due to environmental constraints. The purpose of this study was to determine the extent to which 18 school staff accurately collected DA data with two types of recording formats, narrative and structured, prior to and after receiving a group training that consisted of verbal review and group feedback. Results based on visual analysis indicate that (a) 4 participants engaged in high levels of accurate, narrative DA recording in baseline; (b) 10 of 14 participants reached mastery criteria after training for both narrative and structured DA recording formats; and (c) 4 participants did not reach mastery criteria after training for either recording format. Despite sub-mastery performance by some participants, supplemental statistical analyses and visual inspection indicate that the group training improved all participants’ accuracy from baseline. These findings have important implications for training school staff members to collect DA data.
The Role of a Global Protected Areas System in Conserving Biodiversity in the Face of Climate Change

Impending global change requires levels of coordination, long-range planning and funding never before required of protected areas. To meet this need a truly global system of protected areas is required. This system will require major funding and must ensure the persistence of biodiversity over decades and centuries. It will need to include corridors of semi-natural areas, as well as core parks and reserves. It must be able to ensure the persistence of biodiversity across international boundaries and in spite of international differences in scientific expertise and financing ability. Conservation of species and habitat types has been traditionally framed in a static, two dimensional view, in which reserves are intended to protect these in their present locations. Yet overwhelming evidence exists for major shifts in vegetation in the recent, mid-term and log-term past. The interplay of climate changes and habitat destruction threatens the existing system of isolated reserves. Climate change will create new ranges for many species. Large areas converted to human use, such as agriculture and housing will cut off existing populations from these new ranges. A truly global protected area system does not yet exist. Currently there is a global group of national systems, some of which are connected through information network. Cross border protected areas have existed to protect shared wildlife resources, particularly in Africa, for decades. IUCN regional reviews have provided information to improve protected area network coverage based on regional needs. None of these efforts fully incorporates climate change considerations nor promotes connectivity in the log-term on a global scale. Only a global protected area system which creates corridors between reserves and protects historic locales of habitat suitability can minimize biodiversity loss in the face of climate change and habitat destruction. Currently more than half the habitable surface of the planet is dedicated to human uses. Climate change will be driving vegetation shifts across this landscape. Species with strong dispersal ability will fill new ranges, while slower dispersing species will be unable to STS jump the gap CCH to a new habitat Species with less dispersal ability will become locally extinct, and eventually large-scale loss of biodiversity will occur. A global system will require a global modelling effort, prioritisation, and novel finance mechanisms. A coordinates global modelling system will be required to determine likely biological changes in response to climate change. Base don model results, priority areas for international investment can be selected. Since biodiversity hotspots are predominantly in the temperate countries, a new international protocol and new mechanisms of finance will be required. Finally, because available land for protected areas is nearly exhausted, global financing will have to buy back land and convert it from human use to natural or semi-natural cover in key corridor areas. This paper present a preliminary proposal for such a system.
Scalar Time Functions: Differentiability

It is a pleasure to contribute this paper in honor of Professor Lichnerowicz, whose pioneering efforts in applying global differential geometry to general relativity have had such a rich harvest.
Influence of behavioral state, sex, and season on resource selection by jaguars (Panthera onca): Always on the prowl?

How a predator uses its landscape to move through its territory and acquire prey is a fundamental question for scientific research. The influence of abiotic and biotic factors on space use of large carnivores has profound implications for their future management and conservation. In the Pantanal, Brazil, jaguars (Panthera onca) are the apex predator, but conflicts with cattle depredations pose a risk to their future conservation. We examined whether behavioral state, sex, and season influenced how jaguars used the landscape in the Pantanal. To accomplish this, we radio‐collared four females and six males; radio‐collared jaguars were monitored for 76 radio‐months with 11,787 GPS locations acquired. We developed resource selection functions (RSFs) examining how female and male jaguars used their landscape during three behavioral states (moving, killing native prey, killing cattle) during two seasons (dry, wet). From the RSF models, we found similar variables and relationships of landscape characteristics that jaguars selected for when moving and when depredating native prey and cattle. While moving, jaguars selected for locations that were either in dense cover or very near dense cover, with higher plant diversity and closer to water than available across the landscape. While null models suggested jaguars opportunistically depredated native prey in the dry season and cattle in the wet season, there was some indication they selected for specific landscape characteristics, mainly dense cover when killing cattle in the dry season and native prey in the wet season. Both sexes killed native prey and cattle within dense cover or close to dense cover as expected of an ambush predator. Particular habitat types were not important as long as there was dense cover for concealment. Additionally, jaguars killed prey closer to water than was available on the landscape. The similar variables across the models showed the importance of dense cover and distance to dense cover during all three behavioral states indicating jaguars in the Pantanal were “always on the prowl.” Understanding the spatial requirements for jaguars during the acquisition of native prey and cattle may lead to improved management strategies to allow for continued coexistence of jaguars in an area of traditional cattle production.
Ubiquitous Devices for Chemical Sensing

Widely accepted and deployed commodity consumer products (e.g., laptops, optical disk drives, flatbed scanners, tablets, personal digital assistants, cell phones, wrist watches) as well as high-performance components of consumer products (e.g., micromachined accelerometers, radiofrequency identification tags) present a prominent set of attractive capabilities for advanced sensors. For detection of chemical species in liquids and gases, we take advantage of previously developed, optimized, and mass-produced physical transducers, optoelectronic, radiofrequency identification, and other types of components and rationally combine them with sensing materials to produce new types of chemical sensors. This chapter presents several examples of our recent developments to demonstrate chemical sensors based on mechanical, radiant, and electrical signal-transduction methodologies.
Sociocultural origins of the Oromo national movement in ethiopia

This paper examines social and cultural factors that have necessitated the emergence of the Oromo national movement. Since their incorporation into Ethiopia, the Oromo have lost their autonomous cultural and social developement. The Oromo have become second class citizens and lost political freedom and institutional power. Recently Oromo cultural resistance has been transformed into the Oromo national movement that struggled to redefine the relationship between the Oromo and the Ethiopians. The emergence of intellectual and professional groups in Oromo society has played a decisive role in this transformation
Characteristics and impact of the most-cited palliative oncology studies from 1995 to 2016

Palliative care, as a relatively young field within medicine, has increasingly used original research to validate and standardize its practice. In particular, palliative care has been incorporated into oncology to better address end-of-life decisions and care. The goal of this study is to identify seminal studies in the field of palliative oncology while more broadly characterizing the trends across the literature. The publication databases Scopus and Web of Science were queried using predefined search terms to identify palliative oncology studies published between 1995 and 2016. The 100 most-cited articles from the time periods 1995–2005 and 2006–2016 were selected and analysed for publication data and study content. Palliative oncology studies were found to primarily examine patients with multiple rather than single cancer types and rarely were randomized controlled trials. Early research topics of pain, symptoms, and survival studies have been replaced by the issues of access to care, healthcare utilization, and religion and spirituality. By identifying and analyzing notable studies in palliative oncology, we found areas of research that are commonly investigated or overlooked and identified model studies that highlight the need for additional disease-specific randomized control trials to provide high quality clinical evidence in the field.
Human Anxiety and Noradrenergic Function: Preliminary Studies with Caffeine, Clonidine and Yohimbine

Although several neurotransmitter systems have been implicated in the neurobiology of animal fear and human anxiety1, the focus of the present report in this regard is limited to the noradrenergic system. Several lines of evidence suggest an important role for noradrenergic function in the neurobiology of fear, anxiety, alarm and arousal (for review see Uhde et al.2,3). Redmond and Huang4 demonstrated that electrical and pharmacological activation of the noradrenergic nucleus locus coeruleus (LC) in the monkey produced fear behaviors similar to those occurring during exposure to natural threat in the wild. In addition to these behavioral manifestations of fear during LC activation, Redmond and colleagues4,5 documented temporally-related increases in the levels of noradrenaline and its metabolite, 3-methoxy-4-hydroxy-phenylethylene glycol (MHPG), in the brain, cerebrospinal fluid (CSF) and plasma.
The Microbial Metabolite Trimethylamine N-Oxide Links Vascular Dysfunctions and the Autoimmune Disease Rheumatoid Arthritis

Diet and microbiota each have a direct impact on many chronic, inflammatory, and metabolic diseases. As the field develops, a new perspective is emerging. The effects of diet may depend on the microbiota composition of the intestine. A diet that is rich in choline, red meat, dairy, or egg may promote the growth, or change the composition, of microbial species. The microbiota, in turn, may produce metabolites that increase the risk of cardiovascular disease. This article reviews our current understanding of the effects of the molecule trimethylamine-N-oxide (TMAO) obtained from food or produced by the microbiota. We review the mechanisms of actions of TMAO, and studies that associate it with cardiovascular and chronic kidney diseases. We introduce a novel concept: TMAO is one among a group of selective uremic toxins that may rise to high levels in the circulation or accumulate in various organs. Based on this information, we evaluate how TMAO may harm, by exacerbating inflammation, or may protect, by attenuating amyloid formation, in autoimmune diseases such as rheumatoid arthritis.
Breastfeeding and timing of pubertal onset in girls: a multiethnic population-based prospective cohort study

Early puberty is associated with higher risk of adverse health and behavioral outcomes throughout adolescence and adulthood. US girls are experiencing earlier puberty with substantial racial/ethnic differences. We examined the association between breastfeeding and pubertal timing to identify modifiable risk factors of early puberty and potential sources of racial/ethnic differences in the timing of pubertal development. A prospective cohort study of 3331 racially/ethnically diverse girls born at Kaiser Permanente Northern California (KPNC) between 2004 and 06. All data were obtained from KPNC electronic clinical and administrative datasets. Mother-reported duration of breastfeeding was obtained from questionnaires administered at each ‘well-baby’ check-up exam throughout the baby’s first year and categorized as ‘Not breastfed’, ‘Breastfed < 6 months’, and ‘Breastfed ≥6 months’. Pubertal development data used Tanner stages assessed by pediatricians during routine pediatric checkups starting at age 6. Pubertal onset was defined as transition from Tanner Stage 1 to Tanner Stage 2+ for breast (thelarche) and pubic hair (pubarche). Weibull regression models accommodating for left, right, and interval censoring were used in all analyses. Models were adjusted for maternal age, education, race/ethnicity, parity and prepubertal body mass index (BMI). We also examined race/ethnicity as a potential effect modifier of these associations. Not breastfeeding was associated with earlier onset of breast and pubic hair development compared to breastfeeding ≥6 months (adjusted hazard ratio [HR]: 1.25; 95% confidence interval [CI]: 1.07–1.46; HR: 1.24; 95% CI: 1.05–1.46, respectively). Breastfeeding for < 6 months was also associated with the risk of earlier pubic hair development (HR: 1.14; 95% CI: 1.00–1.30, compared to breastfeeding ≥6 months). Inclusion of girls’ prepubertal BMI slightly attenuated the association between breastfeeding and timing of breast onset but remained significant. The association between not breastfeeding and early breast development may be stronger among African American girls (HR: 1.92; 95% CI: 1.01–3.66, compared to breastfeeding ≥6 months) than other racial/ethnic groups. Breastfeeding is an independent predictor of pubertal onset in girls, and the strength of the association may vary by race/ethnicity. Providing breastfeeding support and lactation education for high risk mothers may help prevent earlier pubertal onset and promote positive health outcomes later in life.
Improvements to mechanical response tissue analysis.

Abstract Cortical Bone Mechanics Technology™ (CBMT) comprises certain improvements over a previous method known as Mechanical Response Tissue Analysis (MRTA). Both methods are dynamic 3-point bending tests intended for measuring the mechanical properties of cortical bone in living people. MRTA presented a theoretical potential for direct measurement of skeletal fragility, but it had acquired a reputation for error and fallen into disuse. We found sources of error in both MRTA data collection and data analysis. We describe here the fundamentals of MRTA, the major sources of error we found in MRTA, and our innovations for avoiding them. • Data collection at many sites across the mid-shaft of the ulna bone in the forearm. • Parameter estimation by fitting analytical complex compliance and stiffness transfer functions to empirical complex compliance and stiffness frequency response functions. • Optimization by selecting results from frequency response functions with the smallest deviations between fits to compliance and stiffness frequency response functions.
Development and preliminary evaluation of an animation (simplifyKDPI) to improve kidney transplant candidate understanding of the kidney donor profile index

Background Transplant candidates are reluctant to accept kidneys from high Kidney Donor Profile Index (KDPI) donors. Incomplete understanding can lead to transplant delays for older transplant candidates. Patients need access to understandable information to make more informed decisions about KDPI. Methods We developed a KDPI-specific animation with input from six stakeholder groups and conducted a one-group pre-post study with 60 kidney transplant candidates for feasibility and acceptability to improve participant KDPI knowledge, understanding, decisional self-efficacy, and willingness to accept a KDPI > 85% kidney. Data were compared using McNemar's test and Wilcoxon signed-rank test. Results Compared with pre-animation scores, post-animation scores were significantly higher for KDPI knowledge for the entire cohort (4.6 vs 6.1, P 85% kidneys (32% vs 36%, P = .83) increased by 2%. After viewing simplifyKDPI, >90% indicated positive ratings on ease of watching, understanding, and engaging. Conclusion In collaboration with stakeholders, an educational animation about KDPI was developed that was well-received and is promising to impact knowledge.
Aggregatibacter actinomycetemcomitans leukotoxin: From mechanism to targeted anti-toxin therapeutics.

Aggregatibacter actinomycetemcomitans is a Gram-negative bacterium associated with localized aggressive periodontitis, as well as other systemic diseases. This organism produces a number of virulence factors, all of which provide some advantage to the bacterium. Several studies have demonstrated that clinical isolates from diseased patients, particularly those of African descent, frequently belong to specific clones of A. actinomycetemcomitans that produce significantly higher amounts of a protein exotoxin belonging to the repeats-in-toxin (RTX) family, leukotoxin (LtxA), whereas isolates from healthy patients harbor minimally leukotoxic strains. This finding suggests that LtxA might play a key role in A. actinomycetemcomitans pathogenicity. Because of this correlation, much work over the past 30 years has been focused on understanding the mechanisms by which LtxA interacts with and kills host cells. In this article, we review those findings, highlight the remaining open questions, and demonstrate how knowledge of these mechanisms, particularly the toxin's interactions with lymphocyte function-associated antigen-1 (LFA-1) and cholesterol, enables the design of targeted anti-LtxA strategies to prevent/treat disease.
Perspectives Toward Seeking Treatment Among Patients With Psoriasis: Protocol for a Twitter Content Analysis.

Background: Psoriasis is an autoimmune disease estimated to affect more than 6 million adults in the United States. It poses a significant public health problem and contributes to rising health care costs, affecting people’s quality of life and ability to work. Previous research showed that nontreatment and undertreatment of patients with psoriasis remain a significant problem. Perspectives of patients toward seeking psoriasis treatment are understudied. Social media offers a new data source of user-generated content. Researchers suggested that the social network Twitter may serve as a rich avenue for exploring how patients communicate about their health issues. Objective: The objective of this study is to conduct a content analysis of Twitter posts (in English) published by users in the United States between February 1, 2016, and October 31, 2018, to examine perspectives that potentially influence the treatment decision among patients with psoriasis. Methods: User-generated Twitter posts that include keywords related to psoriasis will be analyzed using text classifiers to identify themes related to the research questions. We will use Symplur Signals, a health care social media analytics platform, to access the Twitter data. We will use descriptive statistics to analyze the data and identify the most prevalent topics in the Twitter content among people with psoriasis. Results: This study is supported by the National Center for Advancing Translational Science through a Clinical and Translational Science Award award. Study approval was obtained from the institutional review board at the University of Southern California. Data extraction and cleaning are complete. For the time period from February 1, 2016, to October 31, 2018, we obtained 95,040 Twitter posts containing terms related to “psoriasis” from users in the United States published in English. After removing duplicates, retweets, and non-English tweets, we found that 75.51% (52,301/69,264) of the psoriasis-related posts were sent by commercial or bot-like accounts, while 16,963 posts were noncommercial and will be included in the analysis to assess the patient perspective. Analysis was completed in Summer 2020. Conclusions: This protocol paper provides a detailed description of a social media research project including the process of data extraction, cleaning, and analysis. It is our goal to contribute to the development of more transparent social media research efforts. Our findings will shed light on whether Twitter provides a promising data source for garnering patient perspective data about psoriasis treatment decisions. The data will also help to determine whether Twitter might serve as a potential outreach platform for raising awareness of psoriasis and treatment options among patients and implementing related health interventions.
Time-based Assessment of Hearing Preservation Rates After Microsurgical Resection of Vestibular Schwannomas: A Systematic Review.

OBJECTIVE To determine short- and intermediate-term hearing preservation rates after microsurgical resection of vestibular schwannoma (VS). DATA SOURCES Systematic review of the Ovid, Cochrane, EMBASE, and Web of Science databases. STUDY SELECTION This study was restricted to full-text English-language articles detailing VS resection via the middle cranial fossa or retrosigmoid approaches. Documentation of pre- and posttreatment hearing outcomes with American Academy of Otolaryngology-Head and Neck Surgery, Gardner-Robertson, or word recognition score scales, as well as time to follow-up were required. Duplicate data sets, studies with >10% of patients with neurofibromatosis two, previous or nonsurgical VS treatment, case reports with <five patients, or studies detailing decompressive surgery were excluded. DATA EXTRACTION Two authors independently performed full-text reviews to determine study eligibility. Discrepancies were settled by consensus. "Class A/B, I/II" hearing was defined as AAO-HNS Class A or B, Gardner-Robertson Class 1 or 2, or PTA ≤ 50 dB with word recognition score ≥ 50% on audiogram. DATA SYNTHESIS Pooled estimates of preserved Class A/B, I/II hearing at last postoperative follow-up. CONCLUSIONS Of 1323 reports, 14 were utilized in analyses yielding data from 2,977 patients. Mean follow-up was 52.5 months (SD = 19.9). Class A/B, 1/2 hearing was preserved at last follow-up in 57% of patients. Meta-regression revealed that resection through the middle cranial fossa was associated with preservation of serviceable hearing. Moreover, when preserved in the immediate postoperative period, it seems to be stable over time.
Pralatrexate injection for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma.

Peripheral T cell lymphomas (PTCL) are a heterogenous group of lymphoproliferative disorders which are generally not curable with conventional chemotherapy and associated with inferior outcomes. Pr...
The relationship between biofilm formation, genes of virulence and iron metabolism in Escherichia coli

Escherichia coli is known as one of the bacterial species with the widest adaptability to variety of niches either within organisms or outside in environment. Most strains of E. coli are of low virulence and associated with opportunistic infections, whereas others are highly virulent. The success of E. coli in colonising such a wide range of hosts and environments is basically due to a noticeable ductility in exploiting the available resources. It is becoming increasingly clear that biofilms have an enormous impact on medicine because since 65% of animal and human bacterial infections involve biofilms. In present study, we isolated strains of E. coli from animals. 19 interesting isolates were selected and tested by PCR amplification to virulence – iutA, cvaC, iss, tsh, papC, kps, iha and iron metabolism genes – sitA, feoB, irp2, fyuA, iroN, ireA. The ability of biofilm formation was assessed in a quantitative assay using a microtiter-plate test. Bacterial strains were grown on BHI. We divided isolates of E. coli into four classes: very weak (63.0%), weak (10.5%), moderate (10.5%) and strong (16.0%) biofilm producers. Representation genes of virulence were highly in isolates from very weak biofilm producers – from 7 genes were 6 highly; only papC (P fimbrial adhesin) was low. Genes of iron metabolism were different. Genes – sitA, fyuA, ireA in strong isolates producing biofilm and feoB, irp2, iroN in weak producers were most represented. The results show possible relation between presence virulence factor and low biofilm formation.
Written Under the Skin: Blood and Intergenerational Memory in South Africa: by Carli Coetzee, Woodbridge, Suffolk, James Currey/Johannesburg, Wits University Press, 2019, xi + 176 pp.

“This monograph,” Carli Coetzee announces, “uses the image of blood just under the skin to theorise and interpret understandings of the ever emergent present in South Africa …. Blood inside the bod...
Design and Magnetic Field Analysis of a Dual Rotor Axial Flux PM Machine with Steel-Assisted Halbach Magnet Configuration

This paper presents a new magnet configuration for 90° halbach rotors in an axial flux permanent magnet machine which has a reduced permanent magnet material requirement. The designed and optimized steel-assisted halbach rotor produces nearly equal peak torque as one with a conventional 90° halbach array. A generalized analytical method based on Schwarz-Christoffel (SC) conformal transformation is presented for fast magnetic field analysis of the designed machine. Quasi-2D and 3D FEA results are also presented to show the performance of the proposed configuration in comparison to conventional rotor topologies and to validate the results of the SC analytical model.
Imaging as a tool to accelerate the translation of extracellular vesicle-based therapies for central nervous system diseases

Extracellular vesicles (EVs) are natural and diverse lipid bilayer-enclosed particles originating from various cellular components and containing an abundance of cargoes. Due to their unique properties, EVs have gained considerable interest as therapeutic agents for a variety of diseases, including central nervous system (CNS) disorders. Their therapeutic value depends on cell origin but can be further enhanced by enrichment of cargo when used as drug carriers. Therefore, there has been significant effort directed toward introducing them to clinical practice. However, it is essential to avoid the failures we have seen with whole-cell therapy, in particular for the treatment of the CNS. Successful launching of clinical studies is contingent upon the understanding of the biodistribution of EVs, including their uptake and clearance from organs and specific homing into the region of interest. A multitude of noninvasive imaging methods has been explored in vitro to investigate the spatio-temporal dynamics of EVs administered in vivo. However, only a few studies have been performed to track the delivery of EVs, especially delivery to the brain, which is the most therapeutically challenging organ. We focus here on the use of advanced imaging techniques as an essential tool to facilitate the acceleration of clinical translation of EV-based therapeutics, especially in the CNS arena. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease Diagnostic Tools > in vivo Nanodiagnostics and Imaging.
MLDS: A Dataset for Weight-Space Analysis of Neural Networks.

Neural networks are powerful models that solve a variety of complex real-world problems. However, the stochastic nature of training and large number of parameters in a typical neural model makes them difficult to evaluate via inspection. Research shows this opacity can hide latent undesirable behavior, be it from poorly representative training data or via malicious intent to subvert the behavior of the network, and that this behavior is difficult to detect via traditional indirect evaluation criteria such as loss. Therefore, it is time to explore direct ways to evaluate a trained neural model via its structure and weights. In this paper we present MLDS, a new dataset consisting of thousands of trained neural networks with carefully controlled parameters and generated via a global volunteer-based distributed computing platform. This dataset enables new insights into both model-to-model and model-to-training-data relationships. We use this dataset to show clustering of models in weight-space with identical training data and meaningful divergence in weight-space with even a small change to the training data, suggesting that weight-space analysis is a viable and effective alternative to loss for evaluating neural networks.
Cystic Fibrosis Human Organs-on-a-Chip

Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the cystic fibrosis transmembrane regulator (CFTR) gene: the gene product responsible for transporting chloride and bicarbonate ions through the apical membrane of most epithelial cells. Major clinical features of CF include respiratory failure, pancreatic exocrine insufficiency, and intestinal disease. Many CF animal models have been generated, but some models fail to fully capture the phenotypic manifestations of human CF disease. Other models that better capture the key characteristics of the human CF phenotype are cost prohibitive or require special care to maintain. Important differences have been reported between the pathophysiology seen in human CF patients and in animal models. These limitations present significant limitations to translational research. This review outlines the study of CF using patient-derived organs-on-a-chip to overcome some of these limitations. Recently developed microfluidic-based organs-on-a-chip provide a human experimental model that allows researchers to manipulate environmental factors and mimic in vivo conditions. These chips may be scaled to support pharmaceutical studies and may also be used to study organ systems and human disease. The use of these chips in CF discovery science enables researchers to avoid the barriers inherent in animal models and promote the advancement of personalized medicine.
Analysis of an Inelastic Column

An inelastic column that is deformable throughout is analyzed. Simplifying assumptions are that the column is pinned at both ends and is symmetrical about its midspan, the cross section is rectangular, and the material is bilinear. By making certain assumptions about the strain distribution throughout the column, nonlinear differential equations are derived. Solutions of these equations, obtained on a digital computer, are presented.
Investigating Holistic Wellness Dimensions During Older Adulthood: A Factor Analytic Study

The purpose of this study was to examine what dimensions of holistic wellness emerged in a sample of older adults (N = 229) using the Perceived Wellness Survey, and if these dimensions resembled developmental theories of aging. Results from an exploratory principal-axis factor analysis revealed a four-factor solution of holistic wellness: Existential Success, Existential Despair, Physical Wellness, and Future Physical Wellness. Discussion pertaining to how these factor solutions corroborate with the developmental literature is provided, as well as suggestions for further research and humanistic counseling strategies.
Management's Incentives to Guide Analysts' Forecasts

Recent reports in the popular press allege that managers guide analysts' forecasts downward to improve their chances of meeting or beating these forecasts when earnings are announced. Since the majority of this alleged guidance is unobservable, I use systematic patterns in analysts' forecast errors as a proxy for firm-provided guidance and examine both the change in guidance over time as well as the characteristics of firms exhibiting evidence of this guidance. The evidence is consistent with an increase in firm-provided guidance in recent years and differences across firms in the propensity to guide forecasts downward. In particular, I find: 1) an increasing number of forecast errors exactly equal to zero particularly for firms with initially high forecasts; 2) when firms miss analysts' expectations at the earnings announcement, the proportion that miss "high" (positive earnings surprise) versus miss "low" (negative earnings surprise) has increased in recent years particularly for firms with initially high forecasts; 3) firms with higher growth prospects, higher institutional ownership, and higher litigation risk are more likely to guide analysts' forecasts downward to ensure reported earnings meet expectations at the earnings announcement, while firms with low value relevance of earnings are less likely to do so; and 4) firms with high institutional ownership and reliance on implicit claims with their stakeholders tend to exceed rather than fall short of expectations at the earnings announcement.
Chemicals on plant surfaces as a heretofore unrecognized, but ecologically informative, class for investigations into plant defence

Plants produce and utilize a great diversity of chemicals for a variety of physiological and ecological purposes. Many of these chemicals defend plants against herbivores, pathogens and competitors. The location of these chemicals varies within the plant, some are located entirely within plant tissues, others exist in the air- (or water-) space around plants, and still others are secreted onto plant surfaces as exudates. I argue herein that the location of a given defensive chemical has profound implications for its ecological function; specifically, I focus on the characteristics of chemical defences secreted onto plant surfaces. Drawing from a broad literature encompassing ecology, evolution, taxonomy and physiology, I found that these external chemical defences (ECDs) are common and widespread in plants and algae; hundreds of examples have been detailed, yet they are not delineated as a separate class from internal chemical defences (ICDs). I propose a novel typology for ECDs and, using existing literature, explore the ecological consequences of the hypothesized unique characteristics of ECDs. The axis of total or proportional investment in ECDs versus ICDs should be considered as one axis of investment by a plant, in the same way as quantitative versus qualitative chemical defences or induced versus constitutive defences is considered. The ease of manipulating ECDs in many plant systems presents a powerful tool to help test plant defence theory (e.g. optimal defence). The framework outlined here integrates various disciplines of botany and ecology and suggests a need for further examinations of exudates in a variety of contexts, as well as recognition of the effects of within-plant localization of defences.
Pseudomonas Deficient in Protease IV Has Significantly Reduced Corneal Virulence

Purpose The role of protease IV in the pathogenesis of Pseudomonas aeruginosa keratitis was investigated by comparing a mutant strain completely deficient in protease IV activity with its protease IV activity-producing parent. Methods A protease IV-deficient Pseudomonas strain PA103-29::Tn9 was generated by mutagenesis of strain PA103-29, which produces protease IV, through transposon insertion. Protease IV activity was determined by a casein agar assay, zymography, and cleavage of the chromogenic substrate, Chromozym PL. Corneal virulence was evaluated by slit lamp examination and bacterial cultures in both a rabbit intrastromal model and a mouse topical model of keratitis. Results The protease IV-deficient strain PA103-29::Tn9 had significantly reduced corneal virulence relative to its parent strain PA103-29 in both a rabbit intrastromal model and a mouse topical model of infection. In the rabbit model, ocular damage (slit lamp examination score) mediated by the parent strain was severe at 32 hours after infection, whereas damage mediated by the mutant was minimal at both 32 and 55 hours after infection. This difference in virulence was not a result of differences in growth in vivo, because both strains grew equally. In the mouse model, eyes inoculated with the protease IV-producing parent strain had significant corneal damage as early as 24 hours after infection, whereas the protease IV-deficient mutant strain produced no significant corneal damage during 6 days of infection. Conclusions The ability to produce active protease IV was the determining factor in the severity of corneal virulence. Protease IV appears to mediate corneal virulence and should be considered as a target in the development of medications designed to minimize corneal damage during Pseudomonas keratitis.
Are the psychological needs of adolescent survivors of pediatric cancer adequately identified and treated

Objectives To describe the psychological needs of adolescent survivors of acute lymphoblastic leukemia (ALL) or brain tumor (BT), we examined the following: (i) the occurrence of cognitive, behavioral, and emotional concerns identified during a comprehensive psychological evaluation and (ii) the frequency of referrals for psychological follow-up services to address identified concerns. Methods Psychological concerns were identified on measures according to predetermined criteria for 100 adolescent survivors. Referrals for psychological follow-up services were made for concerns previously unidentified in formal assessment or not adequately addressed by current services. Results Most survivors (82%) exhibited at least one concern across domains: behavioral (76%), cognitive (47%), and emotional (19%). Behavioral concerns emerged most often on scales associated with executive dysfunction, inattention, learning, and peer difficulties. Cranial radiation therapy was associated with cognitive concerns, χ2(1, N = 100) = 5.63, p < 0.05. Lower income was associated with more cognitive concerns for ALL survivors, t(47) = 3.28, p < 0.01, and more behavioral concerns for BT survivors, t(48) = 2.93, p < 0.01. Of the survivors with concerns, 38% were referred for psychological follow-up services. Lower-income ALL survivors received more referrals for follow-up, χ2(1, N = 41) = 8.05, p < 0.01. Referred survivors had more concerns across domains than non-referred survivors, ALL: t(39) = 2.96, p < 0.01; BT: t(39) = 3.52, p < 0.01. Trends suggest ALL survivors may be at risk for experiencing unaddressed cognitive needs. Conclusions Many adolescent survivors of cancer experience psychological difficulties that are not adequately managed by current services, underscoring the need for long-term surveillance. In addition to prescribing regular psychological evaluations, clinicians should closely monitor whether current support services appropriately meet survivors' needs, particularly for lower-income survivors and those treated with cranial radiation therapy. Copyright © 2012 John Wiley & Sons, Ltd.
Cultural Issues in the Primary Care of South Asians

One of the fastest growing immigrant groups in the United States is from the Indian subcontinent of South Asia. Included in this group are people from India, Sri Lanka, Bangladesh, and Pakistan. Although there is considerable heterogeneity within and between the populations of these countries, cultural similarities contribute to common challenges when South Asian immigrants are seen in primary care settings in the United States. This article describes aspects of the South Asian culture and of the acculturation process relevant to establishing rapport and providing competent biopsychosocial care to individuals and families from this region. We discuss the differing needs of recent immigrants, second-generation Americans from South Asia, and individuals temporarily in the United States for study or employment. We discuss linguistic and interpersonal style concerns in regard to the relationship between health care professionals and immigrant patients and use case material to illustrate cultural issues. We conclude with suggestions for culturally sensitive health care of South Asians.
Towards Verification of Model Transformations Via Goal-Directed Certification

Embedded software is widely used in automotive applications, often in critical situations where reliability of the system is extremely important. Such systems often use model based development approaches. Model transformation is an important step in such scenarios. This includes generating code from models, transforming design models into analysis models, or transforming a model between variants of a formalism (such as variants of Statecharts). It becomes important to verify that the transformation was correct, and the transformed model or code preserved the semantics of the design model. In this paper, we will look at a technique called "goal-directed certification" that provides a pragmatic solution to the verification problem. We will see how we can use concepts of bisimulation to verify whether a certain transformation instance preserved certain properties. We will then extend this idea using weak bisimulation and semantic anchoring, to a more general class of transformations.
MIL-100 derived nitrogen-embodied carbon shells embedded with iron nanoparticles

The use of metal-organic frameworks (MOFs) as templates and precursors to synthesize new carbon materials with controllable morphology and pre-selected heteroatom doping holds promise for applications as efficient non-precious metal catalysts. Here, we report a facile pyrolysis pathway to convert MIL-100 into nitrogen-doped carbon shells encapsulating Fe nanoparticles in a comparative study involving multiple selected nitrogen sources. The hierarchical porous architecture, embedded Fe nanoparticles, and nitrogen decoration endow this composite with a superior oxygen reduction activity. Furthermore, the excellent durability and high methanol tolerance even outperform the commercial Pt-C catalyst.
Chemical constituents of fruit of cocculus carolinus D. C. (menispermaceae)

Abstract A phytochemical investigation of an ethanolic extract of the fruit of Cocculus carolinus resulted in the isolation and characterization of the alkaloids, cocculolidine and cocculine. The cyclitols (+)‐quercitol and (‐)‐viburnitol and the alkaloids carococculine, magnoflorine, and palmatine, previously reported in the stems and leaves of this species, were also isolated and identified.