cssi/SciSciGPT-SciSciNet huggingface dataset:
On-Manifold GMM Registration

This letter presents a robust Gaussian mixture model registration technique to enable mapping and navigation in dark, complex, unstructured domains such as caves and mines. Subterranean environments are often unmapped and challenged by low-lighting conditions and communication constraints. Prior works that leverage direct and image-based techniques with active illumination fail when taking tight turns due to sensor washout, dense methods are sensitive to initialization, and state-of-the-art registration methods that leverage probabilistic models are neither real-time viable nor thoroughly evaluated with real-world data. The proposed approach minimizes the squared L2 norm between two distributions through an on-manifold parameterization of the objective function. The contribution of this letter is a robust, real-time viable distribution-to-distribution registration methodology that considers all possible correspondences between mixture components. The approach is evaluated in a feature-scarce mine, unstructured cave, and on open-source data of an office environment with both light detection and ranging (LIDAR) and depth sensors. The results demonstrate superior performance as compared to the state of the art. Beyond cave and mine environments, the method readily extends to solving the problem of registration in cluttered domains.
Pupillary response: cognitive effort for breast cancer survivors

The purpose of this cross-sectional comparative pilot study was to evaluate cognitive effort, indexed by pupillary response (PR), for breast cancer survivors (BCS) with complaints of cognitive dysfunction following chemotherapy. Compare the cognitive effort employed by BCS to healthy controls (HC) during neuropsychological tests (NPT) for memory, sustained attention, verbal fluency, visuospatial ability, processing speed and executive function; and Investigate the relationship between PR-indexed cognitive effort and participants’ self-report of cognitive function. Self-report of cognitive function was collected from 23 BCS and 23 HC. PR was measured during NPT. Independent two-sample t tests or Wilcoxon rank sum tests were used to compare group scores. Between-group effect size (Cohen’s d) was calculated for each outcome. Correlation between mean self-report scores and PR values, as well as 95% confidence intervals, was calculated. No group differences were demonstrated for NPT performance. BCS reported more issues with cognitive function than HC (p < .0001). A group effect for BCS was seen with PR-indexed cognitive effort for components of most NPT (p < .05). PR was correlated with most self-report measures of cognitive function (r = 0.33–0.45). PR sensitivity to cognitive effort across a variety of NPT and correlation with self-report of cognitive function was demonstrated. The portability, affordability, and “real-time” aspects of PR are attractive for potential use in the clinic setting to assess cognitive function. A larger study is needed to confirm these results. Prospective investigation of PR in BCS is needed to demonstrate sensitivity to cognitive function changes over time.
Indigenous Australians and Resource Access: Comparative Analysis of Inclusive Policies

Despite Australia’s ratification of the United Nations Declaration of the Rights of Indigenous Peoples (UNDRIP) in 2009, Aboriginal peoples continue to face obstacles in exercising their inherent rights to self-determination and to free, prior and informed consent regarding the development of their traditional land. Recent decades have seen advancements in legislation and government-backed programming to support the recognition of Aboriginal peoples’ land rights; however, the current framework often fails to achieve meaningful outcomes for impacted communities. This paper provides an overview of Australia’s current legislative and programming efforts to secure Aboriginal peoples’ land rights, evaluating the benefits and downsides to each initiative from a rights-based perspective, with the aim of promoting productive discourse on pathways to protecting and implementing the rights enshrined in the UNDRIP.
Variation in Righting Times of Holothuria atra, Stichopus chloronotus, and Holothuria edulis in Response to Increased Seawater Temperatures on Heron Reef in the Southern GBR

Sea cucumbers can mitigate some impacts of climate change through digestion of benthic sands and production of calcium carbonate. The projected ecological benefits of sea cucumbers in warmer, more acidic oceans are contingent on the capacities of individuals to acclimate and populations to adapt to climatic changes. The goal of this experiment was to evaluate the degree to which warming waters would impact three abundant species of sea cucumbers on the Heron Reef in Queensland, Australia. We conducted a behavioral assay using three species of sea cucumbers, Holothuria atra, Stichopus chloronotus, and Holothuria edulis. Individuals from each species were subjected to three conditions mimicking current summer temperatures, current winter temperatures, and an elevated temperature consistent with future ocean warming by the year 2100. Sea cucumber reactions were evaluated using righting time as a proxy for their stress levels and overall tolerance of warming events. The three sea cucumber species reacted differently to water temperature changes: H. atra’s righting times declined with temperature, S. chloronotus had greater righting times at high and low temperature extremes, and H. edulis’s righting times remained relatively constant throughout. Our results suggest that each of these species might respond differently to ocean warming and while some may be able to continue to combat climate change in benthic communities, others may decline in ecological function.
On being psychotic in the South Seas, circa 1947

This article tells the story of an anthropologist and a research subject who encountered each other in the middle of the 20th century on an island in the southwestern Pacific. In the midst of an in...
Anthocyanin Delphinidin Prevents Neoplastic Transformation of Mouse Skin JB6 P+ Cells: Epigenetic Re-activation of Nrf2-ARE Pathway

Redox imbalance is a major contributor to the pathogenesis of melanoma and nonmelanoma skin cancer. Activation of the nuclear factor E2–related factor 2 (Nrf2) antioxidant responsive element (ARE) pathway is an intrinsic defense mechanism against oxidative stress. Flavonoids such as anthocyanidins, which are found abundantly in fruits and vegetables, have been shown to activate Nrf2. However, the epigenetic and genetic mechanisms by which anthocyanidins modulate the Nrf2-ARE pathway remain poorly understood in the context of skin cancer. In this study, delphinidin, one of the most potent and abundant anthocyanidins in berries, significantly inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)–induced neoplastic cell transformation in mouse epidermal JB6 P+ cells by 69.4 to 99.4%. The mechanism was elucidated based on observations of increased ARE-driven luciferase activity and elevated mRNA and protein expression of Nrf2 downstream genes, such as heme oxygenase-1 (Ho-1), in JB6 P+ cells. Activation of the Nrf2-ARE pathway was correlated with demethylation of 15 CpG sites in the mouse Nrf2 promoter region between nt − 1226 and − 863 from the transcription start site. The reduced CpG methylation ratio in the Nrf2 promoter region was consistent with observed decreases in the protein expression of DNA methyltransferases 1 (DNMT1), DNMT3a, and class I/II histone deacetylases (HDACs). Overall, our results suggest that delphinidin, an epigenetic demethylating agent of the Nrf2 promoter, can activate the Nrf2-ARE pathway, which can be applied as a potential skin cancer chemopreventive agent.
Synthetic molecular recognition nanosensor paint for microalbuminuria

Microalbuminuria is an important clinical marker of several cardiovascular, metabolic, and other diseases such as diabetes, hypertension, atherosclerosis, and cancer. The accurate detection of microalbuminuria relies on albumin quantification in the urine, usually via an immunoturbidity assay; however, like many antibody-based assessments, this method may not be robust enough to function in global health applications, point-of-care assays, or wearable devices. Here, we develop an antibody-free approach using synthetic molecular recognition by constructing a polymer to mimic fatty acid binding to the albumin, informed by the albumin crystal structure. A single-walled carbon nanotube, encapsulated by the polymer, as the transduction element produces a hypsochromic (blue) shift in photoluminescence upon the binding of albumin in clinical urine samples. This complex, incorporated into an acrylic material, results in a nanosensor paint that enables the detection of microalbuminuria in patient samples and comprises a rapid point-of-care sensor robust enough to be deployed in resource-limited settings. Microalbuminuria, a clinical marker associated with cancer and hypertension, defined by low albumin levels in the urine, is normally detected by immunoassay. Herein, a nanosensor paint was developed using a polymer to mimic fatty acid binding to albumin, transduced by carbon nanotube fluorescence.
Application of Sparse Representation to Beamforming for Direction of Arrival Estimation

A new technique for high-resolution direction of arrival estimation is presented. The method utilizes the traditional beamforming approach and sparse representation to locate signals in single and multiple emitter scenarios. An example is provided where two emitters are spaced 60 degrees apart and then brought closer together, with the performance of the beamforming approach and new approach compared.
We must do better science: addressing racism to improve health and safety for all people.

The brutal killings of George Floyd, Ahmaud Arbery, Breonna Taylor and others sparked widespread protests for racial and economic justice in the USA and around the globe. A fundamental principle espoused by the Black Lives Matter movement and other groups involved in direct action is that our most enduring social problems are rooted in structural factors and must therefore be addressed with structural solutions. (In this context, ‘structural’ refers to elements of social systems that provide a foundation for how societies operate, such as policies, norms, religion and other belief systems and economies.) This principle is as relevant to injury and violence as it is to other health and social problems; disparities in injury outcomes are closely connected to social inequities.1 At this critical point in history, we are called to confront the influence of structural factors on injury and violence directly. Giles and colleagues2 recently recommended that we incorporate equity as the fourth ‘e’ in injury prevention. Building on their recommendation, we argue that it is critical to highlight structural racism as a determinant of injury and violence. Structural racism is at hand …
The Gears of Knowledge Translation: Process Evaluation of the Dissemination and Implementation of a Patient Engagement Toolkit

Patient engagement is a key tenet of patient-centered care and is associated with many positive health outcomes. To improve resources for patient engagement, we created a web-based, interactive patient engagement toolkit to improve patient engagement in primary care across the Veterans Health Administration (VHA). To use the knowledge translation (KT) framework to evaluate the dissemination and implementation of a patient engagement toolkit at facilities across one region in the VHA. Using a mixed-methods approach, this process evaluation involved phone monitoring via semi-structured interviews and group meetings, during which we explored barriers and facilitators to KT. Outcomes were assessed using a structured rubric and existing patient satisfaction measures. We enlisted implementers at 40 VHA facilities primarily serving Pennsylvania, New Jersey, and Delaware to implement patient engagement practices at their sites. Sites were randomly assigned into a high or low coaching group to assess whether external support influenced implementation. Sites with high rubric scores employed and possessed several elements across the KT trajectory from identification of the problem to sustainment of knowledge use. Key factors for successful implementation and dissemination included implementer engagement, organizational support, and strong collaborators. The most frequently cited barriers included short staffing, time availability, lack of buy-in, and issues with leadership. Successful implementers experienced just as many barriers, but leveraged facilitators to overcome obstacles. While sites that received more coaching did not have different outcomes, they were more likely to revisit the toolkit and indicated that they felt more accountable to local personnel. Because leveraging available resources is a key component of successful implementation, future toolkits should highlight the type of facilitators necessary for successful implementation of toolkit content in healthcare settings. The ability to tailor interventions to local context is critical for overcoming barriers faced in most healthcare settings.
Preexposure prophylaxis strategies for African-American women affected by mass incarceration.

Objective We aimed to determine the effectiveness of various pre-exposure prophylaxis (PrEP) prescription strategies for African American women impacted by mass incarceration within an urban setting. Design An agent-based model was utilized to evaluate prevention strategies in an efficient, ethical manner. By defining agents, their characteristics, and relationships, we assessed population-level effects of PrEP on HIV incidence. Methods We tested hypothetical PrEP prescription strategies within a simulation representing the African American population of Philadelphia, Pennsylvania. Four strategies were evaluated: PrEP for women meeting CDC indicators regarding partner characteristics, PrEP for women with a recently incarcerated male partner, PrEP for women with a recently released male partner, and couples-based PrEP at time of release. Interventions occurred alongside scale-up of HAART. We evaluated reductions in HIV transmissions, the number of persons on PrEP needed to avert one HIV transmission (NNT), and the resulting proportions of people on PrEP. Results Scenarios prescribing PrEP based on criminal justice system involvement reduced HIV transmissions. The NNT ranged from 147 (couples-based scenario) to 300 (recently released scenario). The percentage of the female population covered by PrEP at any one time ranged from 0.14% (couples-based) to 10.8% (CDC-based). CDC-guideline scenarios were consistently less efficient compared to the justice-involved interventions. Conclusions Expanding PrEP for African American women and their male partners affected by incarceration should be considered in national HIV prevention goals and correctional facilities leveraged as intervention sites. Partner characteristics in the current CDC indications may be more effective and efficient if guidelines considered criminal justice involvement.
Fabaceae (legume) pollen as an anthropogenic indicator in eastern North America

European land-use indicators in North America typically include pollen from Poaceae (grasses), Ambrosia (ragweed), Rumex (dock), and/or Plantago (plantain). A potential complement to this list is Fabaceae (legumes), members of which were introduced by colonists to eastern North America. Historical records show that Trifolium (clover) was widespread from the earliest days of colonization, and several other Eurasian legumes were also introduced for livestock forage by 1840 ce. As an insect-pollinated family with taxa native to the region, Fabaceae is not usually emphasized in palynological reconstructions. However, Plantago is commonly used as an indicator despite being represented by native and insect-pollinated varieties. Likewise, it can be difficult to distinguish between native and introduced Poaceae, yet an increase in grass pollen is generally taken as a disturbance indicator. In order to assess the value of Fabaceae as an indicator of the settlement horizon, the R package neotoma was used to retrieve Fabaceae pollen data from the Neotoma Paleoecology Database to assess regional trends in abundance and for comparison to the usual suite of taxa. Results confirm the possible utility of Fabaceae as an anthropogenic marker in the study area. Two case studies with good chronological control illustrate how all five taxa can be found at the settlement horizon across the study area and over time: a 14C and 210Pb-dated pond in Connecticut anthropogenically impacted by 1700 ce, and a varved lake in Ontario impacted by 1840 ce.
From genetic data and structures to drug development: New approaches to target Eph receptors

Abstract The Eph receptors are the largest receptor tyrosine kinase (RTK) group. The Ephs and their ephrin ligands are expressed in many tissues during development and in the adult organism and play important roles in diverse processes, including neuronal development, vasculogenesis, cell migration, immunity, tumor progression, and metastasis (Klein, 2012; Wilkinson, 2014; Darling and Lamb, 2019; [1] , [2] , [3] ). Understanding the molecular mechanisms of Eph/ephrin signaling requires detailed characterization of the interactions between Ephs and ephrins in health and disease, and of how these interactions promote initiation of downstream signaling (Nikolov et al., 2013; Pasquale, 2008; Kania and Klein, 2016; [4] , [5] , [6] ). In this chapter we review current genomics, structural, molecular, and cellular biology studies aimed at understanding the molecular mechanisms of Eph-mediated signaling. We discuss the roles of Ephs and ephrins in tumor progression, metastasis, and development of therapeutic treatments. We focus on Eph-mediated signaling in tumor cells and discuss how mutations altering specific Eph receptor molecular surfaces can lead to pro-malignant misregulation of signaling. The rapidly expanding patient-derived DNA sequence databases have made it possible to use Eph/ephrin structural information to identify disease-causing (missense) mutations that alter Eph molecular surface regions affecting specific protein-protein interfaces and interactions. Such mutations can cause changes in ligand binding, kinase activation, or Eph clustering, ultimately leading to impaired signaling properties. In this chapter we argue that by studying the role of the different protein-protein interactions and interfaces in healthy tissues and in diseases, including cancer, novel and valuable drug candidates and therapeutic strategies can be developed.
An integrative framework for geometric and hidden projections in three-level fractional factorial designs

Abstract Geometric and hidden projection are two important properties to consider for three-level fractional factorials. The effective development of methods that can address tasks involving both these properties requires a unified design framework that integrates them. We highlight one integrative framework that is based on indicator functions for three-level designs under the linear-quadratic parameterization system. We demonstrate the broad scope and utility of this framework by using it to develop a new procedure for addressing a task comprised of three serial problems in geometric and hidden projection. The first in the series is to construct the sets of smallest follow-up runs to a projection of a three-level design that yield specified aliasing relations. Second is to immediately characterize the partial aliasing relations among factorial effects in the resulting augmented designs. The final problem is to identify the augmented designs that maximize popular optimality criteria with respect to the second-order model among all of the candidate augmentations. The application of our procedure is illustrated with sample projections of definitive screening designs onto four, five, and six factors. The integrative framework that we present can ultimately facilitate the systematic development of methods that advance comprehensive understanding of multiple properties for general three-level designs.
Epidemiology of SLE and related diseases: incidence, prevalence, and mortality

Abstract Recent estimates of the incidence of systemic lupus erythematosus (SLE) vary widely around the world, but mainly fall between 1.4 and 6.3 cases per 100,000 per year. Rates are higher in women than in men, and lowest among whites compared to other ethnic groups. There has been no clear trend in incidence rates over recent years. Prevalence among US whites and many studies from Europe range from 32 to 55 per 100,000, while prevalence among US blacks ranges from 118 to 241 per 100,000. Few large epidemiological studies have been performed in low- or middle-income countries. Standardized mortality ratios indicate a threefold higher risk of death among patients with SLE than the general population. Mortality has decreased over the past several decades.
Validated HIV Knowledge Scales for Use with Adults and Adolescents: A Systematic Review.

HIV knowledge - the information a person possesses about HIV - is essential for the prevention and management of HIV. Therefore, the accurate measurement of HIV knowledge is important for both science and practice. This systematic review identifies extant HIV knowledge scales that have been validated with adolescent and adult populations and summarizes the state of this research. We searched seven electronic databases, which resulted in 6,525 articles. After title/abstract and full-text review, 27 studies remained and underwent qualitative review of reported scale psychometric properties. Many studies were conducted in the last decade (n = 12), reflecting advances in scientific knowledge of HIV. Five were exclusively adolescent-based studies (sample age ≤ 18). Most studies reported reliability (n = 25) or at least one form of validity (n = 21). Future studies should develop or refine HIV knowledge scales so that they reflect recent scientific developments, use rigorous psychometric testing, and target samples that include those persons at highest risk for HIV.
Dissection of the eukaryotic chromosome with deoxyribonucleases.

Publisher Summary This chapter describes the dissection of the eukaryotic chromosomes with deoxyribonucleases. Dissection of the chromosome with a variety of deoxyribonucleases has facilitated the isolation of individual subunits. Analysis of the kinetics of nuclease digestion has permitted the elucidation of the repeating subunit structure (4–10) and has provided information on the internal structure of the nucleosome. Digestion of chromatin from a variety of sources with the enzyme staphylococcal nuclease results in the liberation of about half of the chromatin DNA as acid-soluble oligomers. The associated nucleoprotein fragments contain all of the chromatin proteins but only half the original complement of DNA. The kinetics of digestion of DNA in isolated rat liver nuclei again reveals that about half of the nuclear DNA is susceptible to nuclease attack. The chapter discusses the use of various nucleases to probe the organization of chromatin. General materials and methods are discussed including preparation of nuclei, preparation of chromatin, and nuclease digestions of nuclei and chromatin. Analysis of the DNA products of nuclease digestion and staphylococcal nuclease digestion of nuclei are discussed in the chapter.
Radioimmunoassay for type A toxin of Clostridium botulinum.

A preparation of pure type A toxin of Clostridium botulinum was labeled with /sup 131/I in the presence of chloramine-T and carrierfree isotope. The radioactive toxin (/sup 131/I Tox) was used in a radioimmunoassay procedure similar to that of Berson and Yalow. Dilutions of antibody to the toxin, capable of binding 50% of the added /sup 131/I Tox, were mixed wfth a sample of the labeled toxin and various concentrations of unlabeled toxin ( Cold' Tox). When concentration of Cold Tox were plotted against the ratio /sup 131/I bound/ /sup 131/I not bound, a standard curve was established that could be used to estimate the concentration of Cold Tox in a test minture. This assay was sensitive to as little as 100 mouse minimum lethal dose and was highly specific for the serological type of the toxin used. (auth)
Watermelon, Cantaloupe and Honeydew

Introduction Watermelon (Citrullus lanatus) is adapted to many areas of the world and is grown in 96 countries (National Watermelon Promotion Board [NWPB], 2011). The largest production areas globally are China, Turkey, Iran, the United States, and Spain, respectively (Boriss et al., 2006). There are seeded and seedless genotypes with over a thousand varieties among these genotypes (NWPB, 2011). Watermelons can have a flesh color of white, yellow, orange, pink, red, or mixed red and yellow (Bang et al., 2010). Seeded varieties may be open pollinated (heirloom) or hybrids. In the United States, seedless watermelons make up 95% of the total watermelon acreage. The few seeded watermelons still produced are generally from pollinators used to get seedless watermelons or for traditional (“heirloom”) types favored regionally. Once used as a dessert fruit primarily for its sweet, crisp qualities, watermelon has garnered interest as a source of lycopene and beta-carotene and the nonessential amino acid, arganine precursor, citrulline. These compounds have purported antioxidant and anti-inflammatory activity. Additionally, watermelon is an excellent source of vitamin C and vitamin A (Table 28.1). The total world production of watermelons was 89.15 million metric tons (MMT) in 2010, which reflected over 250% increase as compared to 1990 production of 34.85 MMT (FAO 2011). Leading watermelon-producing countries were China (56.65 MMT), Turkey (3.68 MMT), Iran (3.47 MMT), Brazil 1.87 MMT), and the United States (1.87 MMT). China alone accounted for almost two-thirds of the total watermelons produced in the world (FAO, 2011). Mexico, Spain, the United States, Kazakhstan, and Viet Nam were the leading exporters, and the United States, China, Germany, Canada, and France were the leading importers of watermelon in 2009 (FAO, 2011). Total volume of watermelon used in the United States in 2010 was 11.2 billion kg, with 19% imported, 6% exported, and a value of $460 million (NASS, 2011). US consumption in 2011 was 34.1 kg watermelon per capita; the consumption trends have changed from a seasonal to a yearround fruit, primarily through imports during the winter months.
Chapter 12 Pi-linked anion exchange in bacteria: Biochemical and molecular studies of UhpT and related porters

Publisher Summary This chapter focuses on transport systems that carry out an exchange (antiport) reaction, one of several kinds of secondary transport—that is, a reaction not explicitly associated with chemical or photochemical energy transductions. Membrane carrier proteins involved in such secondary transport are associated with many events in biology, ranging from the accumulation of nutrients and extrusion of wastes by bacteria to the cycling of neurotransmitters at synaptic or synaptosomal membranes. However, whether one considers microbiology or neuroscience, these carrier proteins all share certain basic elements of structure and mechanism. Kinetic patterns embodying the carrier hypothesis can be mapped onto a single physical structure, and the current emphasis is on finding these systems. In this effort, bacterial models may be significant because they are among the most susceptible to a molecular analysis. The chapter presents the currently known examples of Pi-linked antiport. Pi-linked antiporters are identified by work with gram-positive cells, and those prototypes are the best to understand.
Opioid treatment at release from jail using extended‐release naltrexone: a pilot proof‐of‐concept randomized effectiveness trial

Background and Aims Relapse to addiction following incarceration is common. We estimated the feasibility and effectiveness of extended-release naltrexone (XR-NTX) as relapse prevention among opioid-dependent male adults leaving a large urban jail. Design Eight-week, proof-of-concept, open-label, non-blinded randomized effectiveness trial. Setting New York City jails and Bellevue Hospital Center Adult Primary Care clinics, USA. Participants From January 2010 to July 2013, 34 opioid-dependent adult males with no stated interest in agonist treatments (methadone, buprenorphine) received a counseling and referral intervention and were randomized to XR-NTX (n = 17) versus no medication (n = 17) within one week prior to jail release. Intervention XR-NTX (Vivitrol®; Alkermes Inc.), a long-acting injectable mu opioid receptor antagonist. Measures The primary intent-to-treat outcome was post-release opioid relapse at week 4, defined as ≥10 days of opioid misuse by self-report and urine toxicologies. Secondary outcomes were proportion of urine samples negative for opioids and rates of opioid abstinence, intravenous drug use (IVDU), cocaine use, community treatment participation, re-incarceration and overdose. Findings Acceptance of XR-NTX was high; 15 of 17 initiated treatment. Rates of the primary outcome of week 4 opioid relapse were lower among XR-NTX participants: 38 versus 88% [P<0.004; odds ratio (OR) = 0.08, 95% confidence interval (CI) = 0.01–0.48]; more XR-NTX urine samples were negative for opioids, 59 versus 29% (P<0.009; OR = 3.5, 95% CI = 1.4–8.5). There were no significant differences in the remaining secondary outcomes, including rates of IVDU, cocaine use, re-incarceration and overdose. Conclusion Extended-release naltrexone is associated with significantly lower rates of opioid relapse among men in the United States following release from jail when compared with a no medication treatment-as-usual condition.
Inhibition of prostaglandin synthesis fails to prevent gallbladder mucin hypersecretion in the cholesterol-fed prairie dog.

Abstract Gallstone formation in the cholesterol-fed prairie dog is preceded by an increase in mucin secretion by the gallbladder epithelium, and mucin hypersecretion is believed to promote cholesterol gallstone formation by accelerating the nucleation of cholesterol monohydrate crystals. Some studies have suggested that gallbladder mucin hypersecretion is mediated by increases in gallbladder prostaglandin synthesis, but other observations are difficult to reconcile with this view. An organ culture technique was used to measure mucin secretion in normal prairie dog gallbladder in response to exogenous prostaglandins and agents that increased or decreased endogenous prostaglandin production. Incubation with indomethacin produced a concentration-dependent inhibition of endogenous prostaglandin synthesis with virtually complete inhibition at 10 −5 mol/L indomethacin. However, indomethacin had no effect on gallbladder mucin secretion at concentrations as high as 10 −5 mol/L, and significant inhibition of mucin secretion was only found at 10 −4 mol/L indomethacin, a concentration that also produced a significant increase in lactate dehydrogenase release from cultured explants. Incubation of gallbladder explants with the calcium ionophore A23187 significantly stimulated endogenous prostaglandin synthesis in a concentration-dependent manner, increasing synthesis of prostaglandins E and F to as much as 278% ± 20% and 335% ± 21% of basal values, respectively; however, the same concentrations of A23187 did not stimulate mucin secretion. Incubation of gallbladder explants in the presence of exogenous prostaglandin E 2 or prostaglandin F 2a in concentrations as high as 10 −6 mol/L also did not stimulate mucin secretion. Prairie dogs fed a lithogenic 1.2% cholesterol diet showed a significant increase in gallbladder mucin secretion after 1 week (117.5 ± 10.2% of control, P −1 · day −1 , failed to inhibit gallbladder mucin hypersecretion (129.2 ± 10.7% of control after 1 week) or cholesterol monohydrate crystal formation (35) in cholesterol-fed prairie dogs. Furthermore, incubation of explants with 10 −5 mol/L indomethacin failed to prevent in vitro mucin hypersecretion in cholesterol-fed animals. These findings suggest that prostaglandins do not regulate gallbladder mucin secretion in the prairie dog, and it is unlikely that increases in gallbladder prostaglandin synthesis are responsible for mediating gallbladder mucin hypersecretion during cholelithiasis in the prairie dog.
Facile synthesis of deuterated and [14C]labeled analogs of vanillin and curcumin for use as mechanistic and analytical tools

Curcumin is a dietary diphenol with antioxidant, antinflammatory, and antitumor activity. We describe facile procedures for the synthesis of [14C2]curcumin (4 mCi/mmol), [d6]curcumin, [d3]curcumin, [13C5]curcumin, and [d6]bicyclopentadione, the major oxidative metabolite of curcumin. We also describe synthesis of the labeled building blocks [14C]vanillin, [d3]vanillin, and [13C5]acetylacetone. The overall molar yields of the labeled products were 52 ([14C]) and 47% ([d3]) for vanillin and 25 ([14C2]) and 27% ([d6]) for curcumin. The compounds can be used as radiotracers in biotransformation studies and as isotopic standards for mass spectrometry-based quantification in pharmacokinetic analyses. Copyright © 2013 John Wiley & Sons, Ltd.
Targeted test input generation using symbolic-concrete backward execution

Knowing inputs that cover a specific branch or statement in a program is useful for debugging and regression testing. Symbolic backward execution (SBE) is a natural approach to find such targeted inputs. However, SBE struggles with complicated arithmetic, external method calls, and data-dependent loops that occur in many real-world programs. We propose symcretic execution, a novel combination of SBE and concrete forward execution that can efficiently find targeted inputs despite these challenges. An evaluation of our approach on a range of test cases shows that symcretic execution finds inputs in more cases than concolic testing tools while exploring fewer path segments. Integration of our approach will allow test generation tools to fill coverage gaps and static bug detectors to verify candidate bugs with concrete test cases.
Induction of IL-17A Precedes Development of Airway Hyperresponsiveness during Diet-Induced Obesity and Correlates with Complement Factor D

Obesity is a risk factor for the development of asthma. Obese mice exhibit innate airway hyperresponsiveness (AHR), a characteristic feature of asthma, and IL-17A is required for development of AHR in obese mice. The purpose of this study was to examine the temporal association between the onset of AHR and changes in IL-17A during the development of obesity by high-fat feeding in mice. At weaning, C57BL/6J mice were placed either on mouse chow or on a high-fat diet (HFD) and examined 9, 12, 15, 18, or 24 weeks later. Airway responsiveness to aerosolized methacholine (assessed via the forced oscillation technique) was greater in mice fed HFD versus chow for 24 weeks but not at earlier time points. Bronchoalveolar lavage and serum IL-17A were not affected by either the type or duration of diet, but increased pulmonary IL17a mRNA abundance was observed in HFD versus chow fed mice after both 18 and 24 weeks. Flow cytometry also confirmed an increase in IL-17A C gd T cells and IL-17A C CD4 C T (Th17) cells in lungs of HFD versus chow fed mice. Pulmonary expression of Cfd (complement factor D, adipsin), a gene whose expression can be reduced by IL-17A, decreased after both 18 and 24 weeks in HFD versus chow fed mice. Furthermore, pulmonary Cfd mRNA abundance correlated with elevations in pulmonary Il17a mRNA expression and with AHR. Serum levels of TNFa, MIP-1a, and MIP-1b, and classical markers of systemic inflammation of obesity were significantly greater in HFD than chow fed mice after 24 weeks, but not earlier. In conclusion, our data indicate that pulmonary rather than systemic IL-17A is important for obesity-related AHR and suggest that changes in pulmonary Cfd expression contribute to these effects of IL-17A. Further, the observation that increases in Il17a preceded the development of AHR by several weeks suggests that IL-17A interacts with other factors to promote AHR. The observation that the onset of the systemic inflammation of obesity coincided temporally with the development of AHR suggest that systemic inflammation may be one of these factors.
In Search of Innovation: Research on Effective Models of Foreign Language Teacher Preparation

Today's teachers must be more than transmitters of knowledge who orchestrate repetitive practice of decontextualized language forms with students: They need to infuse language instruction with meaning and purpose, design opportunities for interaction within and beyond the classroom, and provide responsive and useful assistance throughout the learning process. This review reveals a paucity of empirical research that provides evidence for models of foreign language teacher preparation with the potential to prepare teachers for this role. Despite this lack of research, this review illustrates how the ACTFL/NCATE Program Standards for the Preparation of Foreign Language Teachers (ACTFL, 2002) may be invoked as a viable framework for identifying the components of effective and innovative foreign language teacher preparation programs, presenting current programs that exemplify those components, and suggesting continued application of the standards and future research to further define features of model teacher preparation.
Type Appraisal: II. Variation in Type Traits Due to Sires, Herds, and Years

Abstract Variance components were estimated from type appraisal data to determine the importance of year, herd, sire, and herd×sire effects upon 49 body, udder, and management traits. Estimates were based on over 16,000 appraisals on daughters of Holstein artificial insemination sires. The variation explained by these effects never exceeded 34% of the total variance. Year effects were almost nonexistent (–2 to 3%). Herd effects were small for all traits except feeding speed, body weight, intensity and persistency of edema, and ketosis, and never exceeded 25%. Most appraisal traits had low heritabilities. The estimate for milking speed was .23 while estimates for other management traits were less than .08. The estimates for body weight and upstanding-ness were .40 and .39. Other body traits having estimates from .16 to .21 were sharpness, height of thurls, depth of body, levelness of rump, tightness of shoulders, and height of tail setting. The heritability estimates for udder traits were low. Estimates for only three of 21 udder traits exceeded .14. These were strength of rear attachment, rear teat spacing, and depth of udder.
Therapeutic approaches to Type 2 diabetes mellitus

Diabetes is a significant healthcare problem worldwide and its incidence is rising. Type 2 diabetes patients are at significant risk of developing additional major diseases, especially obesity, hypertension, and dyslipidaemia. All of these conditions are associated with adverse cardiovascular events including myocardial infarction, stroke, and death. Current research is focused on several distinct classes of pharmacological targets in an effort to identify effective therapies for diabetes. Recently, several antidiabetic agents have been identified that promote anabolism, such as agonists for peroxisome proliferator activated receptor γ (PPARγ) and retinoid X receptor (RXR). PPARγ and RXR are ligand activated transcription factors that form a heterodimeric complex that mediates fat cell differentiation and expression of genes involved in lipid and carbohydrate metabolism. PPARγ and RXR agonists, such as the thiazolidinediones (TZDs) and rexinoids, respectively, improve insulin sensitivity and increase repa...
Low temperature synthesis and characterization of MgO/ZnO composite nanowire arrays

Large scale dendritic MgO/ZnO composite nanowire arrays have been successfully synthesized on Si substrates using a two-step sequential hydrothermal synthesis at low temperature for the first time. X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), scanning transmission electron microscopy (STEM), and x-ray photoelectron spectroscopy (XPS) were systematically carried out to confirm and elaborate the potentially localized Mg surface alloying process into the ZnO nanowire arrays. Both room temperature and low temperature (40 K) photoluminescence results revealed an enhanced and blue-shifted near-band-edge (NBE) ultraviolet (UV) emission for the MgO/ZnO nanowires compared to those of the pure ZnO nanowire arrays, indicating the success of Mg alloying into ZnO nanowires. This enhancement might be due to the 155 °C hydrothermal process and the amorphous MgO layer in the MgO/ZnO nanowires. The specific template of densely packed ZnO nanowire arrays was suggested to be instrumental in enabling this type of MgO/ZnO composite nanowire growth.
A comparison of gravimetric thickness and colour thickness for films of oxide on iron

Abstract A linear relationship between the thicknesses of films of iron oxide and silver iodide of corresponding temper colours is found, but the slope is not the ratio of the refractive indices as theory predicts. By postulating multiple internal reflections before emergence of the internal beam, agreement between theory and experiment is achieved. The postulate also explains the anomalously low absolute values of “gravimetric thicknesses” as compared to “colour thicknesses” for iron oxide films. A surface roughness of 1·6 for iron sheets during oxidation is calculated.
Tilting of the Primordial Power Spectrum with Bulk Viscosity

Within the context of the cold dark matter model, current observations suggest that inflationary models that generate a tilted primordial power spectrum with negligible gravitational waves provide the most promising mechanism for explaining large-scale clustering. The general form of the inflationary potential which produces such a spectrum is a hyperbolic function and is interpreted physically as a bulk viscous stress contribution to the energy momentum of a perfect baryotropic fluid. This is equivalent to expanding the equation of state as a truncated Taylor series. Particle physics models that lead to such a potential are discussed
Oncogenic mutations cause dramatic, qualitative changes in the transcriptional activity of c-Myb

The v-Myb oncoprotein encoded by Avian Myeloblastosis Virus is highly oncogenic, induces leukemias in chickens and mice and transforms immature hematopoietic cells in vitro. The v-Myb protein is a mutated and truncated version of c-Myb, a DNA-binding transcription factor expressed in many cell types that is essential for normal hematopoiesis. Previous studies suggested that two types of differences, DNA binding domain mutations and the deletion of a C-terminal negative regulatory domain were important for increasing the transforming activity of v-Myb. Here, we combined structure-function studies of the v-Myb and c-Myb proteins with unbiased microarray-based transcription assays to compare the transcriptional specificities of the two proteins. In human cells, the v-Myb and c-Myb proteins displayed strikingly different activities and regulated overlapping, but largely distinct sets of target genes. Each type of mutation that distinguished v-Myb from c-Myb, including the N- and C-terminal deletions, DNA binding domain changes and mutations in the transcriptional activation domain, affected different sets of target genes and contributed to the different activities of c-Myb and v-Myb. The results suggest that v-Myb is not just a de-repressed version of c-Myb. Instead, it is a distinct transcriptional regulator with a unique set of activities.
Specific features of the determination of residual stresses in paint coatings by the method of bending of plates

We analyze the mathematical and methodical errors made by researchers in finding residual stresses in the coatings by the method of bending of plates proposed by methodical recommendations. New formulas are proposed on the basis of the model according to which stresses decrease across the thickness of the coating as the distance from the metallic substrate increases. It is shown that, contrary to the methodical recommendations, for the correct prediction of residual stresses in the coatings on actual products, it is necessary to restrain laboratory plates on both sides after deposition of the coatings and leave them straight until the complete polymerization (polycondensation) or drying of the material of the coating.
Chemohormonal therapy for advanced breast cancer with tamoxifen, adriamycin, and cyclophosphamide (TAC).

Combined chemohormonal therapy is an attractive therapeutic strategy for the treatment of Stage IV breast cancer. Between 1977 and 1979, the authors evaluated a new chemohormonal therapy program in 63 evaluable women with advanced breast cancer who previously had not received cytotoxic chemotherapy or tamoxifen. The chemohormonal therapy consisted of 21- to 28-day cycles of tamoxifen (10 mg orally twice daily), Adriamycin (doxorubicin) (40 mg/m2 intravenously on day 1) and cyclophosphamide (200 mg/m2 orally on days 3-6) (TAC). Objective responses were observed in 82% of the patients (22% complete response, 60% partial response). With a median follow-up of 104 weeks (2 years), the median relapse-free survival for the 52 responding patients was 80 weeks. The median survival for the entire group of 63 patients was 118 weeks. Eleven pretreatment patient characteristics were evaluated via univariate and multivariate analysis to determine their effect on response and survival. Prognostic factors with a significant association with longer survivals were as follows: a lack of soft tissue involvement, a lack of pleural involvement, and a long disease-free interval (DFI). Estrogen receptor (ER)-unknown patients, being composed primarily of postmenopausal patients with a long DFI and single-organ involvement (primarily bone), comprised 62% of the patient population and achieved a survival similar to the smaller number of ER-positive patients and was superior to the survival of ER-negative patients. Toxicities were recorded on all patients and overall the treatment was well tolerated. Combined chemohormonal therapy with TAC resulted in a high objective response rate and a long median survival. This study would support additional trials of chemohormonal therapy in patients with ER-positive tumors or in those whose tumors are likely to be ER-positive (e.g., postmenopausal patients with long DFIs).
Reactions of the dirhenium(II) complexes Re2X4(dppm)2 (X = Cl or Br; dppm = Ph2PCH2PPh2) with tertiary phosphine and phosphite ligands. The isolation and characterization of the 1:1 adducts Re2X4(dppm)2(PR3) and Re2Cl4(dppm)2[P(OR)3] and the crystal structure of [Re2Cl3(dppm)2(NCEt)2]PF6

Abstract The triply bonded complexes Re2X4(dppm)2 (X = Cl or Br; dppm = Ph2PCH2PPh2) react with PMe3 to afford the 1:1 adducts Re2X4(dppm)2(PMe3) which may have the A-frame-like structure X2Re(μ-X)(μ- dppm)2ReX(PMe3). Similar complexes have been isolated from the reaction of Re2Cl4(dppm)2 with P(OR)3 (R = Me, Et or Ph). The PMe3 ligand of Re2Cl4(dppm)2(PMe3) is quite labile, reaction with nitrile ligands affording the complexes [Re2Cl3(dppm)2(NCR)2]PF6. The structure of a crystal of the propionitrile derivative [Re2Cl3(dppm)2(NCEt)2]PF6·2CH2Cl2 has been determined by X-ray crystallography. This complex crystallizes in the tetragonal space group P 4 21c with a = b = 16.432(2), c = 24.450(4) A, V = 6601(3) A3 and Z = 4. The structure was refined to R = 0.039 (Rw = 0.052) for 1435 data with I>3.0σ(I). The structure of the dirhenium cation can be represented as [(EtCN)2ClRe(μ-dppm)2ReCl2]+, with a ReRe distance of 2.2661(9) A.