cssi/SciSciGPT-SciSciNet huggingface dataset:
Survey on status of occupational health management of 1283 enterprises in Changzhou City

[Objective]To understand the status of occupational health management of enterprises in Changzhou City.[Methods] The questionnaire survey was conducted in 1 283 enterprises that had carried out the occupational hazards network declaration.[Results]The rate of occupational hazards evaluation for constructive project was lower than 20%,and 62.2% of enterprises set up or appointed an occupational health management department.74.5% of enterprises elaborated the occupational hazards in labor contract.The rate of occupational health training in the large and medium-sized enterprises,and small enterprises was 91.5% and 83.2% respectively,and the difference was significant(P 0.05).The rate of occupational hazards evaluation for constructive project in the foreign enterprises and domestic enterprises was 32.2% and 17.3% respectively,and the difference was significant(P 0.05).[Conclusion]In the Changzhou City,the rate of occupational health training in the large and medium-sized enterprises is significantly higher than that in the small enterprises,and the rate of occupational hazards evaluation for constructive project in the foreign enterprises is significantly higher than that in the domestic enterprises.In general,the occupational health management of enterprises in Changzhou City is weak,so the enterprises should pay attention to the occupational health management.
Survey on Current Status of Application of EPI Vaccines in Xiangxi Tujia and Miao Autonomous Prefecture

Objective To investigate the current status of expansion of immunization program after launching the Expanded Programme on Immunization(EPI) in Xiangxi Tujia and Miao Autonomous Prefecture since 2008,and to provide a scientific basis for further developing immunization strategies.Methods Proportion probability sampling(PPS) method was applied to investigate 1,200 children born in 2008 and 2009 and randomly selected from 40 towns(district offices) and 120 administrative villages(neighborhood committees) in Xiangxi Tujia and Miao Autonomous Prefecture.The relative information of the immunization units and vaccination status of the children were surveyed.Results The full course vaccination rate of basic five vaccines(BCG,OPV,DPT,HepB,and MV) was 95.08%.After adding hepatitis A vaccine,epidemic cerebrospinal meningitis vaccine,and Japanese encephalitis vaccine,the full course vaccination rate of eight vaccines was 79.73%.The annual average income of epidemic preventive professionals was RMB 23,000 yuan.Among these professionals,full-time staff accounted for 58.72%,the specialists with certified qualification and with qualification certificate accounted for 56.88% and 73.39%,respectively.Conclusions The immunization coverage rate of basic five vaccines(BCG,OPV,DPT,HepB,and MV) maintained a high level in Xiangxi Tujia and Miao Autonomous Prefecture.But the immunization coverage rates of hepatitis A vaccine,epidemic cerebrospinal meningitis vaccine,Japanese encephalitis vaccine,and the boosting regimes were lower,the immunization units lacked professional and technical personnel and their income were too low.It is necessary to increase professional and technical personnel and strengthen the management.
Reduction of snoring with a plasma-mediated radiofrequency-based ablation (Coblation) device.

We evaluated the effectiveness of using a plasma-mediated radiofrequency-based ablation (Coblation) device to perform volumetric tissue reduction of the soft palate as a means of controlling snorin...
MRI assessment of aortic flow and pulse wave velocity in response to exercise

Background The effect of exercise on cardiac function is important in the diagnosis of cardiovascular disease [1], yet is clinically not available with MRI. Instead, pharmacological agents are used, which have several disadvantages [2]. Recent work has addressed this shortcoming with an MR compatible ergometer next to the magnet [3], albeit with an unavoidable time delay between exercising and actual scanning, which can reduce the measured effect. In this pilot study, we investigated flow and area changes in the aorta with customized exercise equipment that functions in the bore.
Stress Measurements and Processing Optimization for Solution Derived SrBi2Ta2O9 Thin Films

The development of stress in the SrBi2Ta2O9 (SBT) films generated from a chemical solution deposition method was monitored during processing using wafer curvature measurements. Stress measurements of the entire Si/SiO2/Pt/SBT stack revealed an overall tensile stress of ∼536 MPa. The greatest increase in tensile stress was recorded for the anneal of the Pt bottom electrode and was due to the thermal expansion mismatch. Deposition of an amorphous SBT layer on the Pt, followed by a low temperature anneal (300°C), had little overall effect on the stress of the stack; however, upon crystallization, significantly more tensile stress was introduced into the stack. To further investigate the effect that stress has on the various electrical properties SBT films, wafers with different stress states were produced and SBT films deposited on them. Initial investigations indicate that SBT films on wafers with a higher tensile stress displayed improved ferroelectric hysteresis and switchable polarization.
Gas Chromatographic Analysis of Pesticide Residues Containing Phosphorus and/or Sulfur with Flame Photometric Detection and Some Ancillary Techniques for Verifying their Identities

In our efforts to diminish insect depredation of food and fiber, insecticides continue to be our primary weapon. The persistent chlorinated hydrocarbons have now been largely replaced by organophosphorus and carbamate insecticides because they are bio-degradable and do not tend to accumulate in animal tissues and to generally pollute the environment.
Optic Nerve Sheath Diameter Measurement During Diabetic Ketoacidosis: A Pilot Study.

Diabetic ketoacidosis-related cerebral edema (DKA-CE) occurs in up to 1% of children with type 1 diabetes (T1D),1 with approximately 20% displaying neurologic symptoms at presentation.2,3 Similarly, up to 54% have a mild form of subclinical DKA-CE identified by extracellular fluid measurements on magnetic resonance imaging (MRI), which is associated with alterations in neuronal function and cerebral injury on MR spectroscopy.2–6 This suggests that DKA-CE occurs along a continuum, ranging from asymptomatic imaging changes, mild neurologic injury, to cerebral herniation and death. DKA-CE is currently assessed by clinical symptoms and advanced imaging techniques, which have significant cost and limitation. Computed tomography (CT) uses ionizing radiation and can miss nearly 40% of children who ultimately develop DKA-CE.7 MRI is time-consuming, often requires sedation, and may not be available at some centers. Moreover, both CT and MRI require moving critically ill patients out of the intensive care setting. In contrast, point-of-care ocular ultrasound is a relatively low cost, accessible imaging technique that may have the potential to promptly identify DKA-CE through measurement of the optic nerve sheath diameter (ONSD). The sonographic appearance of the ONSD correlates with elevations in intracranial pressure (ICP), which is thought to be due to cerebrospinal fluid accumulation between the dura and optic nerve with the subsequent appearance of swelling.8 ONSD measurement has been used to accurately detect increased ICP in a number of clinical situations,8–10 including pediatric head trauma11 and hydrocephalus.12,13 This method has also been validated in adults using direct measurements of ICP via intrathecal infusion tests,14 lumbar puncture,15 and intracranial monitoring.16 The point at which patients actually progress to subclinical DKA-CE and the minimum duration of preceding symptoms has not been delineated.7 Furthermore, it is currently unclear how the ONSD changes during T1D-related illness or whether ONSD measurement can discriminate stages along the continuum of DKA-CE development, particularly among those with subclinical DKA-CE or those without obvious neurologic symptoms. Therefore, we sought to perform a pilot study among patients with T1D and DKA to determine how ONSD measurements vary during T1D-related illness, and the potential of this tool for discrimination of subclinical DKA-CE. We hypothesized that mean binocular ONSD would increase with illness severity, and would differ among children with DKA, T1D with hyperglycemia, and well-controlled T1D. The association of mean binocular ONSD with DKA-CE risk factors was also examined.
Pregnane X Receptor Regulates Pathogen-Induced Inflammation and Host Defense against an Intracellular Bacterial Infection through Toll-like Receptor 4

The nuclear pregnane X receptor (PXR) plays a central role in regulating xenobiotic metabolism. We now report a novel role for PXR as a critical negative regulator of innate immunity after infection. Pxr−/− mice exhibited remarkably elevated pro-inflammatory cytokine and chemokine production following infection with Listeria monocytogenes (Lm). Despite the more robust innate immune response, Pxr−/− mice were highly susceptible to Lm infection. Surprisingly, disruption of the Toll-like receptor 4 (TLR4) but not TLR2 signaling restored the inflammation to normal levels and the ability to clear Lm in Pxr−/− mice. Mechanistically, the heightened inflammation in Pxr−/− mice resulted in the death of inflammatory monocytes that led to the enhanced susceptibility to Lm infection. These data demonstrated that PXR regulated pathogen-induced inflammation and host defense against Lm infection through modulating the TLR4 pathway. In summary, we discovered an apical role for PXR in regulating innate immunity. In addition, we uncovered a remarkable negative impact of the TLR4 pathway in controlling the quality of the inflammatory response and host defense against a gram-positive bacterial infection.
Measuring Student Growth: A View from the Classroom

Drawing on his own experience as a teacher evaluated by student growth measures (SGMs) in Tennessee, as well as his study of nine Teacher Incentive Fund (TIF) sites around the country that have employed SGMs for consequential decision-making purposes, the author examines the opportunities and challenges of using SGMs for consequential personnel decisions. This chapter focuses on two critical questions: How do teachers and principals understand and use SGMs? What part, if any, should SGMs play in human capital management strategies to improve teaching?
Health literacy: a cross-disciplinary study in American undergraduate college students

Our research aims to assess the health literacy of undergraduate college students. Past research on the health literacy of undergraduate students has revealed some gaps in the undergraduate health literacy. In this study, we employed the Newest Vital Sign Test to measure health literacy. We interviewed 235 undergraduate students from health majors (nursing and other health) and non-health majors. We hypothesised that due to the specificity of a health-related curriculum, nursing and other health-related majors would score higher in health literacy than non-health-related majors, and that nursing majors in particular would score higher than other health-related majors and non-health-related majors. We found support for our hypothesis, as nursing majors had a mean score of 3.57, while health and non-health majors had a mean score of 3.24 and 2.88 respectively when assessing their health literacy levels. We discuss our results with regard to the strategies for improving health literacy skills.
Highly nonlinear solitary waves to estimate the modulus of concrete with different water-to-cement ratios

We describe the feasibility of a nondestructive evaluation (NDE) method for concrete based on the propagation of highly nonlinear solitary waves (HNSWs) along a one-dimensional chain of spherical particles placed in contact with the concrete to be tested. The chain is part of a built-in transducer designed and assembled to excite and detect HNSWs. The method exploits the dynamic interaction between the particles and the concrete. The hypothesis is that the interaction depends on the stiffness of the concrete and influences the time of flight and amplitude of the solitary pulses reflected at the transducer/concrete interface, and traveling within the chain. The results show that the time of flight is monotonically dependent upon the modulus of elasticity of the concrete and that the transducers designed and assembled in this study are reliable and repeatable. In the future, the proposed NDE method may potentially serve as a cost-effective tool for the rapid evaluation of existing concrete structures.
Data interface buffer compensation scheme for fast calibration

Microprocessors and FPGAs need to enable simpler and compact platforms via integration of self-contained test and training circuits, training of data interface buffers for process and temperature variation being a prime example. This paper studies package embedding of resistors for buffer tuning and presents a scheme to utilize a single resistor to train a large number of buffers without increase in latency. Using SNR analysis, transient noise simulations and the consequent filtering latencies it is shown that embedding the compensation resistor on the package reduces the calibration time by 5µs while also reducing the filter size by a factor of 10.
TWEAK mediates inflammation in experimental atopic dermatitis and psoriasis

Atopic dermatitis (AD) and psoriasis are driven by alternate type 2 and type 17 immune responses, but some proteins might be critical to both diseases. Here we show that a deficiency of the TNF superfamily molecule TWEAK (TNFSF12) in mice results in defective maintenance of AD-specific T helper type 2 (Th2) and psoriasis-specific Th17 cells in the skin, and impaired expression of disease-characteristic chemokines and cytokines, such as CCL17 and TSLP in AD, and CCL20 and IL-19 in psoriasis. The TWEAK receptor, Fn14, is upregulated in keratinocytes and dermal fibroblasts, and TWEAK induces these cytokines and chemokines alone and in synergy with the signature T helper cytokines of either disease, IL-13 and IL-17. Furthermore, subcutaneous injection of recombinant TWEAK into naive mice induces cutaneous inflammation with histological and molecular signs of both diseases. TWEAK is therefore a critical contributor to skin inflammation and a possible therapeutic target in AD and psoriasis.
Functional perturbation of forebrain principal neurons reveals differential effects in novel and well-learned tasks.

Abstract Neural circuits in mammalian brains consist of large numbers of different cell types having different functional properties. To better understand the separate roles of individual neuron types in specific aspects of spatial learning and memory, we perturbed the function of principal neurons in vivo during maze performance or in hippocampal slices during recording of evoked excitatory synaptic potentials. Transgenic mice expressing the Drosophila allatostatin receptor (AlstR) in cortical and hippocampal pyramidal cells were tested on an elevated plus maze, in a Y-maze, and in the Morris water maze. Relative to a control cohort, AlstR-positive mice treated with allatostatin exhibited no difference in open arm dwell time on the elevated plus maze or total number of arm entries in a Y-maze, but displayed reduced spontaneous alternation. When animals received massed or spaced training trials in the Morris water maze, and the peptide was delivered prior to an immediate probe, no effects on performance were observed. When the peptide was delivered during a probe trial performed 24 h after seven days of spaced training, allatostatin delivery to AlstR positive mice enhanced direct navigation to the escape platform. Combined, these results suggest that cortical and hippocampal pyramidal neurons are required during spatial decision-making in a novel environment and compete with other neural systems after extended training in a long-term reference memory task. In hippocampal slices collected from AlstR positive animals, allatostatin delivery produced frequency dependent alterations in the Schaffer collateral fiber volley (attenuated accommodation at 100 Hz) and excitatory postsynaptic potential (attenuated facilitation at 5 Hz). Combined, the neural and behavioral discoveries support the involvement of short-term plasticity of Schaffer collateral axons and synapses during exploration of a novel environment and during initial orientation to a goal in a well-learned setting.
Structural and functional insights into the role of BamD and BamE within the β-barrel assembly machinery in Neisseria gonorrhoeae

The β-barrel assembly machinery (BAM) is a conserved multicomponent protein complex responsible for the biogenesis of β-barrel outer membrane proteins (OMPs) in Gram-negative bacteria. Given its role in the production of OMPs for survival and pathogenesis, BAM represents an attractive target for the development of therapeutic interventions, including drugs and vaccines against multidrug-resistant bacteria such as Neisseria gonorrhoeae. The first structure of BamA, the central component of BAM, was from N. gonorrhoeae, the etiological agent of the sexually transmitted disease gonorrhea. To aid in pharmaceutical targeting of BAM, we expanded our studies to BamD and BamE within BAM of this clinically relevant human pathogen. We found that the presence of BamD, but not BamE, is essential for gonococcal viability. However, BamE, but not BamD, was cell-surface–displayed under native conditions; however, in the absence of BamE, BamD indeed becomes surface-exposed. Loss of BamE altered cell envelope composition, leading to slower growth and an increase in both antibiotic susceptibility and formation of membrane vesicles containing greater amounts of vaccine antigens. Both BamD and BamE are expressed in diverse gonococcal isolates, under host-relevant conditions, and throughout different phases of growth. The solved structures of Neisseria BamD and BamE share overall folds with Escherichia coli proteins but contain differences that may be important for function. Together, these studies highlight that, although BAM is conserved across Gram-negative bacteria, structural and functional differences do exist across species, which may be leveraged in the development of species-specific therapeutics in the effort to combat multidrug resistance.
High-throughput genotyping-by-sequencing facilitates molecular tagging of a novel rust resistance gene, R 15 , in sunflower ( Helianthus annuus L.)

A novel rust resistance gene, R 15 , derived from the cultivated sunflower HA-R8 was assigned to linkage group 8 of the sunflower genome using a genotyping-by-sequencing approach. SNP markers closely linked to R 15 were identified, facilitating marker-assisted selection of resistance genes. The rust virulence gene is co-evolving with the resistance gene in sunflower, leading to the emergence of new physiologic pathotypes. This presents a continuous threat to the sunflower crop necessitating the development of resistant sunflower hybrids providing a more efficient, durable, and environmentally friendly host plant resistance. The inbred line HA-R8 carries a gene conferring resistance to all known races of the rust pathogen in North America and can be used as a broad-spectrum resistance resource. Based on phenotypic assessments of 140 F2 individuals derived from a cross of HA 89 with HA-R8, rust resistance in the population was found to be conferred by a single dominant gene (R 15 ) originating from HA-R8. Genotypic analysis with the currently available SSR markers failed to find any association between rust resistance and any markers. Therefore, we used genotyping-by-sequencing (GBS) analysis to achieve better genomic coverage. The GBS data showed that R 15 was located at the top end of linkage group (LG) 8. Saturation with 71 previously mapped SNP markers selected within this region further showed that it was located in a resistance gene cluster on LG8, and mapped to a 1.0-cM region between three co-segregating SNP makers SFW01920, SFW00128, and SFW05824 as well as the NSA_008457 SNP marker. These closely linked markers will facilitate marker-assisted selection and breeding in sunflower.
Micronutrient metal speciation is controlled by competitive organic chelation in grassland soils

Abstract Many elements are scarcely soluble in aqueous conditions found in high pH environments, such as calcareous grassland soils, unless complexed to strong binding organic ligands. To overcome this limitation, some plants and microbes produce chelators that solubilize micronutrient metals such as Fe, Ni, Cu, and Zn from mineral phases. These complexes are taken up by organisms via specific membrane receptors, thereby differentially impacting the bioavailability of these metals to the plant and microbial community. Although the importance of these chelation strategies for individual organisms has been well established, little is known about which pathways coexist within rhizosphere microbiomes or how they interact and compete for metal binding. Identifying these metallophores within natural ecosystems has remained a formidable analytical challenge due to the vast diversity of compounds and poorly defined metabolic processes in complex soil matrices. Herein, we employed recently developed liquid chromatography (LC) mass spectrometry (MS) methods to characterize the speciation of water-soluble dissolved trace elements (Fe, Ni, Cu, and Zn) of soils from native tallgrass prairies in Kansas and Iowa. Both plant and fungal metallophores were identified, revealing compound-specific patterns of chelation to biologically essential metals. Numerous metabolites typically implicated in plant Fe acquisition and homeostasis, including mugineic acids, deoxymugineic acid, nicotianamine, and hydroxynicotianamines, dominated the speciation of divalent metals such as Ni, Cu, and Zn (2–90 pmol/g soil). In contrast, the fungal siderophore ferricrocin was specific for trivalent Fe (7–32 pmol/g soil). These results define biochemical pathways that underpin the regulation of metals in the grassland rhizosphere. They also raise new questions about the competition of these compounds for metal binding and their bioavailability to different members of the rhizosphere population. Small structural modifications result in significant differences in metal ligand selectivity, and likely impact metal uptake within the rhizosphere of grassland soils.
Disorders of Intestinal Absorption

The multiple functions of the small intestine may be subverted and lead to absorptive disorders. This chapter presents a variety of intestinal absorptive diseases, and discusses modes of diagnosis and treatment for the diseases. There are two major groups of absorptive disorders: (1) those disorders because of maldigestion of nutrients in the intestinal lumen or at the mucosal brush border and (2) those disorders because of malabsorption of properly digested nutrients as a result of abnormalities in the intestinal mucosa. Maldigestion and malabsorption often coexist as a result of one process being secondary to the other or both processes being caused by a single agent. Maldigestion occurs because of luminal deconjugation of bile acids, and malabsorption because of patchy inflammatory atrophy of the villous epithelium. Bacterial overgrowth syndromes are examples of the malabsorption.
Electing peace: from civil conflict to political participation, by Aila Matanock

The international community has a major role to play in establishing enduring peace in violence torn societies. Not only through peacekeepers, troops on the ground or masses of foreign aid. In this...
Conjoint Behavioral Treatment of an Alcoholic and His Spouse

The role of the spouse in the treatment of alcohol abuse and alcoholism has been a controversial one. Early models, based on psychodynamic conceptualizations of alcoholic marriages, suggested that spouses of alcoholics were conflicted, needy, neurotic people, who needed intensive individual treatment in order to resolve their own neurotic conflicts (e.g., Price, 1945). Later, sociologically oriented theories suggested that wives of alcoholics were coping with an acute stress. Organizations such as Al-Anon were seen as an excellent modality to provide supportive intervention (e.g., Jackson, 1954). In the 1970s, general systems therapists and behavior therapists both suggested that alcohol problems and marital discord were integrally related, and that modifications of the marital system were perhaps necessary to effect change in an alcoholic’s drinking behavior (e.g., Miller, 1976; Ward & Faillace, 1970).
Understanding and Translating Bilirubin Structure

By the end of the second millennium A.D., nearly 100 years after Nencki and Kuster had initiated the first meaningful degradation of bilirubin (208, 244) that set into motion its eventual structure elucidation, the constitutional and stereochemical structure of the pigment had been solved.
Compactified Strings and the Heterotic Theories

The topics of this lecture are: (1) showing how infinite-dimensional Kac-Moody affine algebras can be spectrum generating algebras in (open) string theories, work I did with Louise Dolan [1]; (2) examining the spectrum of excited states of the heterotic string [2]; and (3) commenting on representations of affine algebras. Ule consider bosonic string models in D dimensions with d of the dimensions being a d-torus. The d-torus is a model for the compactified dimensions. After studying open strings, where the string formalism is quite simple, we look at the heterotic string, which is a closed string model with some formal similarities to the open string. The heterotic string appears to be consistent when interactions are included (the one loop amplitudes are finite and the integrands are modular invariant), and the gravitational and Yang-Mills anomalies cancel. “Part” of the heterotic string is a closed bosonic string in 26 dimensions and part is a closed superstring in 10 dimensions. We compute the spectrum for the E8X E8 version in 10 dimensions; the same methods can be used to analyze the Spin(32)/ℤ2 model.
On–Line Dynamic Analysis of Mechanical Systems

By working with a symbol manipulation computer program created specifically for this purpose, a dynamicist can use a personal computer to analyze motions of mechanical systems in a highly efficient manner. The theory underlying the computer program is discussed, and illustrative examples are presented.
THE IMPACT OF THE ATP-GENERATING SYSTEMS

Publisher Summary This chapter presents the study of the impact of the ATP-generating systems. It discusses the importance of the ATP-generating technique first used by Severo and a few years later recommended by him to Sarah Ratner who developed, refined, and popularized its use for the studies in biosynthesis of urea and to indicate how with its help many reactions that were at the time poorly understood, were clarified. The acceptance of ATP-generating systems suffered a time-delay element as is generally the case for new findings in biochemistry or in any other science. The best indication of scientific success is when a finding loses its primary identification and is absorbed by and becomes a part of the overall body of knowledge; then it is truly a part of science. The first demonstration of ATP coupling to a synthetic reaction was the study by the late John Speck of glutamine synthesis.
Carrier Lifetime and Charge Separation in K+-Doped CZTS Nanocrystals

Cu2ZnSnS4 (CZTS) nanocrystals are important materials for next generation solar energy capture and conversion strategies. CZTS contains earth-abundant materials and has optimum band gap energy and ...
Particle embolization for hemoptysis in two patients with cyanotic congenital heart disease

Abstract Hemoptysis is a known manifestation of complex cyanotic congenital heart disease (CCHD) often related to bleeding from systemic to pulmonary collateral vessels, commonly referred to as aortopulmonary collaterals (APCs). While catheter-directed particle embolization has been historically utilized to treat arterial bleeds causing hemoptysis in other scenarios, coil and vascular plug embolization has been used more frequently to occlude parent arteries in CCHD patients given the concern for shunting of embolic particles. Recently, some centers have shifted to distal particle embolization in treating APCs given its advantages over proximal embolization, including ease of re-treatment if hemoptysis recurs. We describe our experience with distal particle embolization in two CCHD patients experiencing recurrent hemoptysis from APCs following proximal device embolization, highlighting the challenges in endovascular management of these patients.
FDOT: A Fast, memory-efficient and automated approach for Discrete adjoint sensitivity analysis using the Operator overloading Technique

Abstract A new toolbox based on operator overloading is introduced for automatic differentiation of scientific computing codes – and in particular legacy computational fluid dynamics solvers that are developed using Fortran. The method can be readily implemented into existing iterative solvers with minimal changes to the primal code. The integrated toolbox can efficiently calculate the sensitivities of any objective function with respect to all variables (design or intermediate) that can later be used for gradient-based design optimization, uncertainty quantification, error estimation, and mesh adaptation. The underlying definition of the current automatic differentiation is directly related to the discrete adjoint sensitivity analysis. Unlike most traditional operator overloading-based adjoint approaches reported in the literature, the current technique offers huge reductions in the memory footprint. To demonstrate the advantages of the current approach, various solvers/problems are considered. It is shown that the proposed technique can be used as an efficient toolbox for automatic differentiation of scientific solvers requiring only a handful additional lines of coding.
Calyciphylline B-type Alkaloids: Evolution of a Synthetic Strategy to (−)-Daphlongamine H

We provide a full account of our synthetic studies targeting the hexacyclic calyciphylline B-type alkaloids, a subfamily of the Daphniphyllum natural products. Following an initial set of synthetic strategies focused on constructing the piperidine core of the calyciphylline B-type framework via a 6π-azaelectrocyclization, as well as exploiting the reactivity of underexplored oxazaborinine heterocycles, we ultimately designed a highly functionalized acyclic precursor which underwent carefully orchestrated and efficient cyclizations to forge the architecturally complex natural product scaffold. Our efforts have culminated in the development of the first total synthesis of (-)-daphlongamine H, provided access to its C5-epimer, (-)-isodaphlongamine H, and led to structural revision of deoxyisocalyciphylline B.
Association of Genetic Ancestry With DNA Methylation Changes in Prostate Cancer Disparity.

BACKGROUND We hypothesized that ancestry-mediated methylated DNA changes may drive racial and ethnic disparity in prostate cancer (PCa). To test this hypothesis, we analyzed genetic ancestry and association with DNA methylation changes in PCa disparity. MATERIALS AND METHODS Pyrosequencing and ancestry informative markers were used for DNA methylation and genetic ancestry testing, respectively. RESULTS Using Spearman rho rank correlation test, the data demonstrated significant (p<0.05) and variable association between African-American ancestry and DNA methylation for all genes investigated in prostate tissues. CONCLUSION Genetic ancestry influences DNA methylation and this modifying factor must be considered in epigenetic association studies in populations of admixed patients.
APOE genotype regulates pathology and disease progression in synucleinopathy

Apolipoprotein E (APOE) e4 genotype is associated with increased risk of dementia in Parkinson's disease (PD), but the mechanism is not clear, because patients often have a mixture of α-synuclein (αSyn), amyloid-β (Aβ), and tau pathologies. APOE e4 exacerbates brain Aβ pathology, as well as tau pathology, but it is not clear whether APOE genotype independently regulates αSyn pathology. In this study, we generated A53T αSyn transgenic mice (A53T) on Apoe knockout (A53T/EKO) or human APOE knockin backgrounds (A53T/E2, E3, and E4). At 12 months of age, A53T/E4 mice accumulated higher amounts of brainstem detergent-insoluble phosphorylated αSyn compared to A53T/EKO and A53T/E3; detergent-insoluble αSyn in A53T/E2 mice was undetectable. By immunohistochemistry, A53T/E4 mice displayed a higher burden of phosphorylated αSyn and reactive gliosis compared to A53T/E2 mice. A53T/E2 mice exhibited increased survival and improved motor performance compared to other APOE genotypes. In a complementary model of αSyn spreading, striatal injection of αSyn preformed fibrils induced greater accumulation of αSyn pathology in the substantia nigra of A53T/E4 mice compared to A53T/E2 and A53T/EKO mice. In two separate cohorts of human patients with PD, APOE e4/e4 individuals showed the fastest rate of cognitive decline over time. Our results demonstrate that APOE genotype directly regulates αSyn pathology independent of its established effects on Aβ and tau, corroborate the finding that APOE e4 exacerbates pathology, and suggest that APOE e2 may protect against αSyn aggregation and neurodegeneration in synucleinopathies.
Aberrant axonal pathfinding and exuberant myelination in an inducible model of neocortical heterotopia

Neocortical heterotopia consist of ectopic neuronal clusters that are frequently found in individuals with cognitive disability and epilepsy. However, their pathogenesis remains poorly understood due in part to a lack of tractable animal models. We have developed an inducible model of focal heterotopia that enables their precise spatiotemporal control and high-resolution optical imaging in live mice. Here we report that heterotopia are associated with striking patterns of hypermyelinated and circumferentially projecting axons around neuronal clusters. Despite their aberrant axonal patterns, in vivo calcium imaging revealed that heterotopic neurons remain functionally connected to other brain regions, highlighting their potential to influence global neural networks. These aberrant patterns only form when heterotopia are induced during a critical embryonic temporal window, but not in early postnatal development. Our model provides a new way to investigate heterotopia formation in vivo and revealed features suggesting the existence of developmentally-modulated, neuron-derived axon guidance and myelination factors.
Multiscale Modeling of Human Skin Oil-Induced Indoor Air Chemistry: Combining Kinetic Models and Molecular Dynamics

We performed classical molecular dynamics simulations to quantify and understand the nonreactive, dermal uptake of volatile organic compounds formed during the ozonolysis of human skin oils. Our results include surface accommodation coefficients, partitioning constants, bulk diffusivities, and desorption lifetimes. These parameters were used to improve and to constrain the kinetic multilayer model of the surface and bulk chemistry of skin (KM-SUB-Skin). By comparing common outputs (bulk accommodation coefficients), we cross-validate the two approaches and, thus, increase the level of trust in their predictions relevant to indoor air chemistry.
Chapter 222 – Farnesyltransferase Inhibitors

Publisher Summary This chapter deals with farnesyltransferase inhibitors. Inhibitors of farnesyltransferase (FTase), FTIs, have been designed for use as anti-Ras and anti-cancer drugs, but in fact they are selective for FTase, not for Ras. This distinction has important implications for their use as pharmacological tools to dissect signaling pathways. FTIs have been used to implicate Ras in numerous cellular processes, including cell transformation, mitogenesis, neurite outgrowth, motility/migration, response to oxidative stress, transcriptional regulation, and protein secretion. Further, contributions of specific downstream Ras effectors, such as Raf/MEK/Erk, PI3K/Akt, and upstream Ras activators such as receptor tyrosine kinases have also been implicated by using FTIs. However, interpretation of this data has been problematic. Originally designed to treat Ras-related cancers by inhibiting oncogenic Ras function, FTIs are now thought to be ineffective against N- and K-Ras due to alternative prenylation, and to exert their effects primarily through inhibition of the farnesylation of other substrate proteins or the induction of proteins such as RhoB. With so many potential FTI targets, each with a different cellular function and sensitivity to FTIs, the task of unraveling the mechanism of FTI action is complex. But even in the absence of an understanding of which specific substrates mediate which specific consequences, it is clear that FTIs do have utility as anti-cancer agents, and can be useful tools to demonstrate the contribution of farnesylated proteins to the control of a particular signaling pathway.
The Impact of Adherence to Clinical Practice Guidelines on Medical Costs

Objective To examine the association between non-adherence to clinical practice guidelines (CPGs) and medical and indemnity spending among back and shoulder injury patients. Methods Workers compensation claims data was used from a large, US insurer (1999 to 2010). Least square regression models were created to examine the association between spending and guideline-discordant care. Results Non-adherence to CPGs was associated with higher medical and indemnity spending for 11 of the 28 CPG indicators. Failure to adhere to the other CPGs did not increase medical or total spending. After covariate adjustment, non-adherence to these 11 CPGs was associated with spending increases that ranged from $16,000 for physical therapy (PT) to $114,000 for surgery. Conclusions Our results demonstrate that failure to adhere to a subset of CPG indicators significantly predicts increased medical and indemnity spending for two important occupational injuries.
Aluminum-doped U3Si2 composite fuels with enhanced oxidation resistance

Abstract Al-doped U3Si2 composite fuels with controlled microstructure were fabricated by spark plasma sintering that display greatly-improved oxidation resistance as compared with monolithic and Al-doped silicides prepared by standard powder metallurgy or arc melting. The effects of Al additives on the thermal-mechanical properties and oxidation resisance of the micron- and nano-sized U3Si2 composites were investigated. A minimal addition of 1.8 at% Al is effective to increase the onset oxidation temperature of as-fabricated U3Si2 pellets to 580 °C, which can be further increased to 610 °C by thermal annealing. The Al-doped U3Si2 composite fuels also display simultaneously higher hardness and fracture toughness than un-doped U3Si2. These results highlight an effective strategy by integrating minimal Al additives, microstructure control and post-thermal annealing to design advanced silicide fuels with excellent oxidation resistance, desired thermal-mechanical properties and maintained high fissile element density.
A semiparametric method for evaluating causal effects in the presence of error-prone covariates.

The goal of most empirical studies in social sciences and medical research is to determine whether an alteration in an intervention or a treatment will cause a change in the desired outcome response. Unlike randomized designs, establishing the causal relationship based on observational studies is a challenging problem because the ceteris paribus condition is violated. When the covariates of interest are measured with errors, evaluating the causal effects becomes a thorny issue. We propose a semiparametric method to establish the causal relationship, which yields a consistent estimator of the average causal effect. The method we proposed results in locally efficient estimators of the covariate effects. We study their theoretical properties and demonstrate their finite sample performance on simulated data. We further apply the proposed method to the Stroke Recovery in Underserved Populations (SRUP) study by the National Institute on Aging.
Immunometabolic targeting of NK cells to solid tumors

Abstract The function of natural killer cells in tumors is often impaired due to metabolic adaptations of cancer cells, which causes reprogramming of natural killer cell effector and metabolic functions in favor of impaired immunity. As a result, targeting natural killer cells to solid tumors grapples with cells that meet a hostile environment unable to support effector functions. This not only results in cancers that are able to evade targeting, but also promotes natural killer cell dysfunction, most commonly manifested through altered phenotypic and functional signatures. In this chapter, we review the key elements driving natural killer cell metabolism, highlight the role of metabolism in supporting their function against solid tumors, and discuss targeting strategies to drive natural killer cells to solid tumors for immunotherapy.
La verdad práctica en Santo Tomás de Aquino

This paper analyses two texts of Aquinas (Summa theologiae, I-II, q. 57, a. 5, ad 3, and Expositio libri peryermeneias I, 3, 107 ss.) where the truth of practical intellect is defined in accordance with Aristotle's account in Nicomachean Ethics, 1139a27-31. The proposed interpretation tries to show that both texts are arguably not incompatible. A last important claim is that according to the definition of practical truth practical intellect is supposed to work as a mesure for reality.
Carbon dioxide utilization in concrete curing or mixing might not produce a net climate benefit

Carbon capture and utilization for concrete production (CCU concrete) is estimated to sequester 0.1 to 1.4 gigatons of carbon dioxide (CO2) by 2050. However, existing estimates do not account for the CO2 impact from the capture, transport and utilization of CO2, change in compressive strength in CCU concrete and uncertainty and variability in CCU concrete production processes. By accounting for these factors, we determine the net CO2 benefit when CCU concrete produced from CO2 curing and mixing substitutes for conventional concrete. The results demonstrate a higher likelihood of the net CO2 benefit of CCU concrete being negative i.e. there is a net increase in CO2 in 56 to 68 of 99 published experimental datasets depending on the CO2 source. Ensuring an increase in compressive strength from CO2 curing and mixing and decreasing the electricity used in CO2 curing are promising strategies to increase the net CO2 benefit from CCU concrete. Carbon curing or mixing in concrete is promising for carbon dioxide sequestration. Here, the authors show that the increased use of binder material to compensate the loss in compressive strength and electricity for carbon dioxide curing is more likely to increase carbon dioxide emissions on a life cycle basis for carbon cured or mixed concrete.
Combining information within and between pedigrees for mapping complex traits

This paper is concerned with efficient strategies for gene mapping using pedigrees containing small numbers of affecteds and identity-by-descent data from closely spaced markers throughout the genome. Particular attention is paid to additive traits involving phenocopies and/or locus heterogeneity. For a sample of pedigrees containing a particular configuration of affecteds, e.g., pairs of siblings together with a first cousin, we use a likelihood analysis to find 1-df statistics that are very efficient over a broad range of penetrances and allele frequencies. We identify configurations of affecteds that are particularly powerful for detecting linkage, and we show how pedigrees containing different numbers and configurations of affecteds can be efficiently combined in an overall test statistic.
Hierarchical modeling in spatial epidemiology

This paper considers the basic concepts and methods used in hierarchical modeling for data arising in spatial epidemiology. Following discussion of basic statistical and epidemiological concepts relevant to small-area health studies, the paper reviews the different approaches to model formulation, parameter estimation, and also software resources. WIREs Comput Stat 2014, 6:405–417. doi: 10.1002/wics.1315 For further resources related to this article, please visit the WIREs website. Conflict of interest: The author has declared no conflicts of interest for this article.
Some Properties of an Apoceruloplasmin-like Protein in Human Serum

Abstract Rabbit antibody to apoceruloplasmin has been used to demonstrate that two forms of ceruloplasmin occur in serum. In addition to the well known blue protein, a colorless component was found. The latter protein lacks oxidase activity, has a relatively low copper content, and is immunologically similar to apoceruloplasmin. It constitutes from 10 to 20% of the total ceruloplasmin found in normal serum. The electron paramagnetic resonance spectra of ceruloplasmin and its antibody precipitate were found to be identical. Therefore, antibodies could be used to isolate ceruloplasmin from serum for electron paramagnetic resonance studies. An antibody precipitate of all of the ceruloplasmin from a sample of serum contained two species of paramagnetic copper. The colorless ceruloplasmin appears to contain the type of copper which gives an electron paramagnetic resonance signal with a broad hyperfine structure.
The Invention of 'Folk Music' and 'Art Music': Emerging Categories from Ossian to Wagner

Introduction 1. Function to origin: national identity and national genius emerge, c.1700-80 2. From pastoral to picturesque: nature, art, and genre in the later eighteenth century 3. Genius versus Art in the creative process: 'national' and 'cultivated' music as categories, 1760-1800 4. The invention of folk modality, 1775-1840 5. 'Folk' and 'tradition': authenticity as musical idiom from the late eighteenth century onward 6. Organic 'art music' and individual original genius: aestheticizing the folk collective 7. Local nation and universal folk: the legacy of geography in musical categories 8. Folk and art music in the modern western world.
Quantitative evaluation of papilledema in pseudotumor cerebri

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