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To assess whether more severe urinary symptoms and poorer quality of life among patients on diuretic therapy are associated with decreased adherence to the diuretic regimen.Participants were recruited via ResearchMatch.org and sent a REDCap survey. The Overactive Bladder Questionnaire-Short Form (OAB-q SF) was used to assess urinary symptom bother and health-related quality of life (HRQL). Participants were asked if they skip diuretic doses due to urinary symptoms with a bivariate (yes or no) outcome. Subgroup analyses of loop vs non-loop diuretic and those taking the diuretic for a cardiovascular indication (hypertension or heart failure) were performed.A total of 4029 surveys were sent, 285 were returned (7.1% response rate), and 279 were included in the study. Fifty-three participants admitted to skipping diuretic doses due to urinary symptoms. Lower HRQL scores were significantly associated with poorer adherence scores among all participants (P .001), among participants taking a loop diuretic (P .001), and among participants with hypertension and heart failure (P .039). Association between symptoms and adherence remained significant after adjustment in the multivariate model for the whole cohort and loop diuretic subgroup but lost significance in the hypertension and heart failure subgroup.Worsening quality of life due to urinary symptoms may be associated with poorer adherence to diuretics, particularly loop diuretics.

Recent innovations in immunoregulatory treatments have demonstrated both the impressive potential and vital role of T cells in fighting cancer. These treatments come at a cost, with systemic side effects including life-threatening autoimmunity and immune dysregulation the norm. Here, we developed an approach to locally synthesize immune therapies and in this way, avoid systemic toxicity. Rather than just encapsulating cytokines, we endowed our nanoparticles with transcriptional and translational machinery to make cytokines locally, in situ, and on demand (activated by light). We demonstrated the capabilities of these particles in vitro and in vivo, in a mouse model of melanoma, and showed that tumor-infiltrating T cells were more highly activated in the context of these "microfactory" particles that make the synthetic cytokine.

Recent innovations in immunoregulatory treatments have demonstrated both the impressive potential and vital role of T cells in fighting cancer. These treatments come at a cost, with systemic side effects including life-threatening autoimmunity and immune dysregulation the norm. Here, we developed an approach to locally synthesize immune therapies and in this way, avoid systemic toxicity. Rather than just encapsulating cytokines, we endowed our nanoparticles with transcriptional and translational machinery to make cytokines locally, in situ, and on demand (activated by light). We demonstrated the capabilities of these particles in vitro and in vivo, in a mouse model of melanoma, and showed that tumor-infiltrating T cells were more highly activated in the context of these “microfactory” particles that make the synthetic cytokine.

Understanding how teachers utilize, adapt, and integrate curriculum is helpful in the development and dissemination of curricular resources to better serve our teachers’ needs. Agricultural and science educators face similar challenges in selecting, adapting, and delivering curricular content in their courses. The data presented here assesses teachers’ perceptions of online curricular resources and their usage by agriculture and science teachers in K-12 classrooms. The specific research objectives were to 1) determine the teacher’s perceptions and usage of online curriculum resources and 2) determine their methods to locate and select web-based curricular resources. Analysis suggests that the curricular needs and utilization may not be discipline-specific, and that needs identified in other disciplines may have applications in agriculture and science classrooms. Teachers utilized Google, Facebook, and other social media platforms to share and locate resources but expressed the need to have better organization and classification of online resources. Resources need to be tagged with state and national standards, have references, and activities that are engaging for students and easily adaptable to teachers’ local needs and styles. Teaching pre-service teachers to better utilize existing curricular resources could lead to improved instruction and student learning while saving time. Further research into the utilization of existing curriculum by both current and pre-service teachers is warranted.

Dysregulation of lipid homeostasis is a precipitating event in the pathogenesis and progression of hepatosteatosis and metabolic syndrome. These conditions are highly prevalent in developed societies and currently have limited options for diagnostic and therapeutic intervention. Here, using a proteomic and lipidomic-wide systems genetic approach, we interrogated lipid regulatory networks in 107 genetically distinct mouse strains to reveal key insights into the control and network structure of mammalian lipid metabolism. These include the identification of plasma lipid signatures that predict pathological lipid abundance in the liver of mice and humans, defining subcellular localization and functionality of lipid-related proteins, and revealing functional protein and genetic variants that are predicted to modulate lipid abundance. Trans-omic analyses using these datasets facilitated the identification and validation of PSMD9 as a previously unknown lipid regulatory protein. Collectively, our study serves as a rich resource for probing mammalian lipid metabolism and provides opportunities for the discovery of therapeutic agents and biomarkers in the setting of hepatic lipotoxicity. The integration of liver and plasma quantitative lipidomic and proteomic data from 107 distinct mouse strains provides important insights into regulators of mammalian lipid metabolism.

An innovative first- and second-year laboratory course sequence is described. The goal of the instructional model is to introduce chemistry and biochemistry majors to the process of research participation earlier in their academic training. To achieve that goal, the instructional model incorporates significant hands-on experiences with chemical instrumentation, beginning in the first semester and continuing through the fourth semester. The model also strives to instill within students an understanding of the social aspects of a working research laboratory, where members enter and gradually change roles based on increased experience and responsibility. An implicit assumption in the instructional model is that students gradually move from verification experiences to more open-inquiry experiences, which mimics the process of joining a working research laboratory. The capstone experience in this model is a laboratory stand-alone course, where students design and implement experiments related to faculty research projects within the department. Ideas for broader implementation of the model at various types of institutions are also suggested. A paper describing the implementation of the model is forthcoming.

Neural crest cells (NCC) are stem cells that generate different lineages, including neuroendocrine, melanocytic, cartilage and bone. The differentiation potential of NCC varies according to the level from which cells emerge along the neural tube. For example, only anterior “cranial” NCC form craniofacial bone, whereas solely posterior “trunk” NCC contribute to sympathoadrenal cells. Importantly, the isolation of human fetal NCC carries ethical and scientific challenges, as NCC induction typically occur before pregnancy is detectable. As a result, current knowledge of NCC biology derives primarily from non-human organisms. Important differences between human and non-human NCC, such as expression of HNK1 in human but not mouse NCC, suggest a need to study human NCC directly. Here, we demonstrate that current protocols to differentiate human pluripotent stem cells (PSC) to NCC are biased toward cranial NCC. Addition of retinoic acid drove trunk-related markers and HOX genes characteristic of a posterior identity. Subsequent treatment with bone morphogenetic proteins (BMPs) enhanced differentiation to sympathoadrenal cells. Our approach provides methodology for detailed studies of human NCC and clarifies roles for retinoids and BMPs in the differentiation of human PSC to trunk NCC and to sympathoadrenal lineages.

This article traces the history of the involvement of the American Young Men's Christian Association (YMCA) with Russian-language publishing from its beginnings to the end of the twentieth century. During the period between the two world wars this was the primary source of Russian Orthodox theological and philosophical literature. In addition, it served as a catalyst for ferment within Orthodoxy by providing a forum for heated debate, especially in the pages of Put’, a unique interdisciplinary journal of Christian thought. The unique role of the YMCA Press in the Russian emigration has been noted in a variety of studies. However, such evaluations usually do not pay attention to the original Protestant leadership of this remarkable Orthodox publishing house, the political impact of its avowedly non-political efforts, and the recent activities of the YMCA Press in Russia and Ukraine after the end of communism. The Press played a major role in preserving an important aspect of prerevolutionary Russi...

Anterior and anterolateral skull base approaches offer the advantages of improved visualization and minimal brain retraction for lesions involving the orbital apex, parasellar regions, and anterior and middle fossa floors. These approaches are seldom used in the pediatric population due to the perceived increase in morbidity and surgical complexity. We report the application of the previously described modified osteoplastic orbitozygomatic (OZ) craniotomy to pediatric neurosurgical cases. This approach offers a number of advantages and is technically straightforward. The results from six pediatric cases are reported. Age ranged from 26 months to 15 years, with a follow-up period of 5 to 22 months. Pathology included craniopharyngioma (three), frontal epidural abscess–subdural empyema with intraorbital extension (one), hypothalamic hamartoma (one), and optic pathway glioma (one). No complications related to the surgical approach were noted. In all cases, good postoperative cosmesis was achieved with excellent realignment of the orbital rim. Temporalis muscle bulk was preserved and symmetric in all cases. The modified osteoplastic OZ craniotomy can be safely and effectively applied to the pediatric population. Advantages include: (1) ease of use; (2) superior exposure and therefore less brain retraction; (3) an easily replaced one-piece bone flap which obviates the need for plating–suturing at the orbital rim; (4) a vascularized bone flap less susceptible to infection; and (5) maintenance of normal temporalis muscle anatomy for improved cosmesis and function.

Research about the effectiveness of different types of feedback in programmed instruction was investigated. Knowledge of results had the least data to support its efficacy. Knowledge of correct responding (KCR) has been shown to be effective in several studies. Elaboration feedback is more effective than KCR, but may require more time of the instructional designer and learner. Delayed and review feedback are no better than KCR. Postfeedback delays show promise and warrant further study. Future research area recommendations include: measures of the approachability of instruction, measures of efficiency, sampling from more diverse populations, research over more extended time frames, and exploring the relationship between performance during instruction and on criterion tests.

Skinner (1958) expressed the need for an increase in the effectiveness and efficiency of education. In particular, he suggested that programmed instruction could provide such efficiency. The present study used a within-subject design to compare the effects of four types of instructional materials; those requiring overt construction responses, overt discrimination responses, covert reading of text with highlighted key words, and covert reading of standard text. The materials requiring overt responding produced greater learning than did the covert reading materials, with or without highlighting. There was no difference found between the two types of overt responding; nor were there differences between the two types of covert reading materials. Thus, this study supports the assumption that overt responding is more effective. However, the overt response materials also required proportionately more time. Therefore, this showed no benefit of overt responding in terms of efficiency.

Audio fingerprinting is an emerging research field in which a song must be recognized by matching an extracted "fingerprinting" to a database of known fingerprints. Audio fingerprinting must solve the two key problems of representation and search. In this paper, we are given an 8192-bit binary representation of each five second interval of a song and therefore focus our attention on the problem of high-dimensional nearest neighbor search. High dimensional nearest neighbor search is known to suffer from the curse of dimensionality, i.e. as the dimension increases, the computational or memory costs increase exponentially. However, recently, there has been significant work of efficient, approximate, search algorithms. We build on this work and describe preliminary results of a probabilistic search algorithm. We describe the data structures and search algorithm used and then present experimental results for a database of 1,000 songs containing 12,217,111 fingerprints.

The N-protonated bismercaptoethanediazacyclooctane serves as a bidentate dithiolate ligand to oxidized Fe(NO)(2) of Enemark-Feltam notation, E-F [Fe(NO)(2)],(9) mimicking Cys-X-Cys binding of Fe(NO)(2) to proteins or thio-biomolecules. The neutral compound is characterized by the well-known g = 2.03 EPR signal which is a hallmark of dinitrosyl iron complexes, DNIC's. The Fe(NO)(2) unit can be removed from the chelate by excess PhS(-), producing (PhS)(2)Fe(NO)(2)(-). Transfer of NO from Fe(H(+)bme-daco)(NO)(2) (nu(NO) = 1740, 1696 cm(-)(1)) to Fe(II) of [(bme-daco)Fe](2) yields the five-coordinate, square-pyramidal N(2)S(2)Fe(NO) (nu(NO) = 1649 cm(-)(1)), where NO is in the apical position. Its isotropic EPR signal at g = 2.05 is consistent with E-F [Fe(NO)](7) formulation. In excess NO, Roussin's red ester-type molecules are formed as dinuclear or tetranuclear species, [(micro-SRS)[Fe(2)(NO)(4)]](n)() (n =1, 2). These well-characterized molecules furnish reference points for positions and patterns in nu(NO) vibrational spectroscopy expected to be useful for in vivo studies of NO degradation of iron-sulfur clusters in ferredoxins.

We describe a new watermarking system based on the principles of informed coding and informed embedding. This system is capable of embedding 1380 bits of information in images with dimensions 240/spl times/368 pixels. Experiments on 2000 images indicate the watermarks are robust to significant valumetric distortions, including additive noise, low-pass filtering, changes in contrast, and lossy compression. Our system encodes watermark messages with a modified trellis code in which a given message may be represented by a variety of different signals, with the embedded signal selected according to the cover image. The signal is embedded by an iterative method that seeks to ensure the message will not be confused with other messages, even after addition of noise. Fidelity is improved by the incorporation of perceptual shaping into the embedding process. We show that each of these three components improves performance substantially.

The photocatalyic oxidation of dichloromethane over TiO2 was studied using in situ FTIR and solid-state NMR (SSNMR) methods. Dichloromethane photodegradation led to the formation of a number of long-lived intermediate species including CO, HCl, phosgene, chloroform, and CCl4 in the presence of oxygen. FTIR studies showed that the reaction rate and product distribution were strongly dependent on the oxygen concentration. Species often thought to be products in the reactions, particularly HCl, CO, and CCl4, were found to degrade to CO2 and H2O under high relative oxygen concentrations. In addition, formyl chloride was identified as a new intermediate, while phosgene was found to have two production channels. SSNMR experiments showed that one of the two phosgene species resides primarily in the gas phase, while the other was associated with the surface. Additional SSNMR studies of the adsorption of dichloromethane showed that a chloromethoxyl species was formed on anatase TiO2. SSNMR experiments were also he...

In pursuit of an analogy between bidentate diphosphane ligands and cis-dithiolato nickel complexes, the easily prepared [bis(mercaptoethane)diazacycloheptane]nickel complex, Ni-1′, has been treated with PdII and NiII sources. With the latter, trinickel species are observed with typical slant-chair structures; for palladium(II) chloride, a basket-type structure is realized in which the floor of the basket is a PdS4 unit and the sides are N2S2 units. One chloride atom is held within the basket at a Pd···Cl distance of 3.26 A. With Pd(NO3)2 as a palladium source, a hexanuclear aggregate in the form of a C4-paddlewheel structure is obtained. In this structure, the N2S2Ni complex serves as a bidentate ligand which bridges two Pd2+ cations at a distance of 3.132 A. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

Square-planar copper(II) and nickel(II) derivatives of the cis-dithiolate N(2)S(2) ligand bis(N,N'-2-mercapto-2-methylpropyl)-1,5-diazocyclooctane, (bme*daco)M, nucleate four Cu(I)Cl moieties, forming M(II)(2)Cu(I)(4)S(4) clusters with unusual triply bridging thiolates, mu(3)-SR, in the topological form of adamantane. As determined by X-ray crystallography, the (bme*daco)M (M = Cu or Ni) metallothiolate serves as a bidentate ligand that bridges four Cu(I) ions, utilizing all lone pairs on sulfurs. Further characterization by electrochemical and electronic spectral measurements suggests greater electron delocalization in the all-copper complex as compared to the NiCu heterometallic complex. Mass spectral data imply that the mixed-metal Ni(II)(2)Cu(I)(4)S(4) is more stable toward CuCl loss than Cu(II)(2)Cu(I)(4)S(4), a result that is corroborated by extraction of Cu(I) by 1,2-bis(diphenylphosphino)ethane in the latter but not the former.

Hydrogen uptake in hydrogenase enzymes can be assayed by H/D exchange reactivity in H(2)/D(2)O or H(2)/D(2)/H(2)O mixtures. Diiron(I) complexes that serve as structural models for the active site of iron hydrogenase are not active in such isotope scrambling but serve as precursors to Fe(II)Fe(II) complexes that are functional models of [Fe]H(2)ase. Using the same experimental protocol as used previously for ((mu-H)(mu-pdt)[Fe(CO)(2)(PMe(3))](2)(+)), 1-H(+) (Zhao et al. J. Am. Chem. Soc. 2001, 123, 9710), we now report the results of studies of ((mu-SMe)(mu-pdt)[Fe(CO)(2)(PMe(3))](2)(+)), 1-SMe(+), toward H/D exchange. The 1-SMe(+) complex can take up H(2) and catalyze the H/D exchange reaction in D(2)/H(2)O mixtures under photolytic, CO-loss conditions. Unlike 1-H(+), it does not catalyze H(2)/D(2) scrambling under anhydrous conditions. The molecular structure of 1-SMe(+) involves an elongated Fe.Fe separation, 3.11 A, relative to 2.58 A in 1-H(+). It is proposed that the strong SMe(-) bridging ligand results in catalytic activity localized on a single Fe(II) center, a scenario that is also a prominent possibility for the enzyme active site. The single requirement is an open site on Fe(II) available for binding of D(2) (or H(2)), followed by deprotonation by the external base H(2)O (or D(2)O).

To report the case of a never-smoker patient whose initial presentation of metastatic nonsmall cell lung carcinoma was with uveal metastasis, which had a dramatic response to targeted biologic therapy with erlotinib (Tarceva) after failing conventional chemotherapy.Case report. A 43-year-old man with uveal metastasis from nonsmall cell lung adenocarcinoma.After failing conventional chemotherapy with carboplatin and taxol, with continued documented rapid growth of the uveal metastasis, treatment was initiated with the targeted biologic agent, erlotinib, which is a protein tyrosine kinase inhibitor of the epidermal growth factor receptor(EGFR). Within 3 days of starting erlotinib, shrinkage of the choroidal lesion was noted, and over the course of the next 3 months, the tumor completely and durably disappeared, with vision improving from hand motion to 20/25. The patient is still alive and well after 3 years, on continued daily oral erlotinib treatment.Erlotinib is a well-tolerated newly available Food and Drug Administration-approved oral targeted biologic agent, which may be beneficial in some patients with uveal metastasis from nonsmall cell lung carcinoma, in which an underlying epidermal growth factor receptor mutation is suspected.

Currently, many producing formations are carbonates and/or depleted sands that are characterized by highly permeable flow paths or vugs. Severe-to-total loss of drilling fluid in these formations is a major concern from both the drilling and reservoir damage perspectives. Conventional particulate lost circulation materials (LCMs), such as acid-soluble ground marble, might not effectively cure severe losses. Furthermore, because the application is in a producing formation, avoiding reservoir damage is a major criterion that any potential solution should satisfy. The "band-width" of available solutions that are both efficient and reservoir friendly is narrow, leading to both high cost and potentially risky drilling practices. A possible solution is using an acid-soluble right-angle-setting composition (RAS-Co) that was developed to provide the industry with a more efficient solution for plugging and isolating producing zones that have high drilling fluid loss rates. RAS-Co is formulated from inorganic, nonhazardous powders and fluids mixed in fresh water or seawater. RAS-Co is engineered to be a low-viscosity (18 to 30 cp) fluid containing small particulates, which allows it to be mixed at the rigsite and pumped through any drillstring configuration. It is designed to react at a specific bottomhole circulating temperature (BHCT) in a consistent and controllable manner with a "right-angle" set. Once it is spotted/placed in the suspected loss zone, it helps eliminate further fluid losses and formation damage. The small particle size distribution acts as a pore-bridging material while in the fluid state, and the right-angle-set characteristic makes the material non-invasive to the formation and allows it to be easily drilled or removed with acid. It can be used in zones with up to 300°F circulating temperature and tolerates up to 50% contamination with water or drilling fluids. This paper describes attributes of RAS-Co along with successful field applications that illustrate it is an effective solution for controlling reservoir damage by helping to stop severe lost circulation events.