Search

In recent years, research has emerged to quantitatively and qualitatively understand occupants' interactions with buildings. However, there has been surprisingly little research on building interfaces and how their design, context (e.g., location), and underlying logic impact their usability and occupants’ perceived control, as well as the resulting comfort and energy performance. Research is needed to better understand how occupants interact with building interfaces in both commercial and residential applications; both applications are important to address as there are many differences in interface types, level of control and understanding, and even expectations of engagement. This paper provides a cursory review and discussion of select common building interfaces: windows, window shades/blinds, thermostats, and lighting controls. The goal of this paper is to review literature related to these human-building interfaces to explore interface characteristics, current design and use challenges, and relationships between building interfaces and occupants. Human-building interface interactions are complex, more research is needed to understand design, use, and characteristics. Common themes emerged throughout the literature review to explain occupant interactions (or lack of interactions) with building interfaces, which included thermal and visual comfort, ease and access of control, interface/control placement, poor interface/control design, lack of understanding, and social-behavioral dynamics.

Gene regulatory divergence between species can result from cis-acting local changes to regulatory element DNA sequences or global trans-acting changes to the regulatory environment. Understanding how these mechanisms drive regulatory evolution has been limited by challenges in identifying trans-acting changes. We present a comprehensive approach to directly identify cis- and trans-divergent regulatory elements between human and rhesus macaque lymphoblastoid cells using assay for transposase-accessible chromatin coupled to self-transcribing active regulatory region (ATAC-STARR) sequencing. In addition to thousands of cis changes, we discover an unexpected number (∼10,000) of trans changes and show that cis and trans elements exhibit distinct patterns of sequence divergence and function. We further identify differentially expressed transcription factors that underlie ∼37% of trans differences and trace how cis changes can produce cascades of trans changes. Overall, we find that most divergent elements (67%) experienced changes in both cis and trans, revealing a substantial role for trans divergence-alone and together with cis changes-in regulatory differences between species., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Rationale: Isotope analysis can be used to investigate the diets of predators based on assimilation of nitrogen and carbon isotopes from prey. Recent work has shown that tissues taken from legs, antennae or abdomen of lobsters can give different indications of diet, but this has never been evaluated for Sagmariasus verreauxi (eastern rock lobster). Work is now needed to prevent erroneous conclusions being drawn about lobster food webs, and undertaking this work could lead to developing non-lethal sampling methodologies. Non-lethal sampling for lobsters is valuable both ethically and for areas of conservation significance such as marine reserves., Method: We evaluated this by dissecting 76 lobsters and comparing δ 13 C and δ 15 N isotope values in antennae, leg and abdomen tissue from the same individuals ranging from 104 to 137 mm carapace length. Stable isotope values were determined using a Europa EA GSL elemental analyser coupled with Hydra 20-20 Isoprime IRMS., Results: We found the abdomen δ 13 C values to be lower than other tissues by 0.3 ± 0.2‰ for antennae tissue and 0.1 ± 0.2‰ δ 13 C for leg tissues, whereas for δ 15 N, no significant difference between tissues was observed. There was no significant effect of lobster size or sex, though we did observe interactions between month and tissue type, indicating that differences may be seasonal. Importantly, the detected range of isotopic variability between tissues is within the range of uncertainty used for discrimination factors in isotopic Bayesian modelling of 0‰-1.0‰ for δ 13 C and 3.0‰-4.0‰ for δ 15 N., Conclusions: We show that S. verreauxi can be sampled non-lethally with mathematical corrections applied for δ 13 C, whereas any tissue is suitable for δ 15 N. Our results indicate that a walking leg is most favourable and would also be the least intrusive for the lobster. The application of non-lethal sampling provides avenues for the contribution of citizen science to understanding lobster food webs and to undertake fieldwork in ecologically sensitive areas such as marine reserves., (© 2022 The Authors. Rapid Communications in Mass Spectrometry published by John Wiley & Sons Ltd.)

Medical settings can be frightening and stressful places for pediatric patients and their families. During the COVID-19 pandemic fear and anxiety associated with receiving medical care increased as medical facilities dramatically altered the way they functioned in attempts to stop the spread of the virus. Certified Child Life Specialists (CCLSs) are medical professionals who provide psychosocial support for pediatric patients and their families by helping them understand and cope with medical procedures and the medical environment. In this role, CCLSs are likely to have important insights into the experiences and needs of pediatric patients and their families during COVID-19. Using a mixed-methods design, 101 CCLSs completed an online survey and 15 participated in follow-up interviews examining their experiences with and observations of children and families in medical environments during the pandemic. Participants emphasized a need to maintain a focus on child- and family-centered care for the well-being of patients and their families. While recognizing the need to socially distance to limit the spread of COVID, participants expressed concern about restrictive policies that did not balance the physical and mental health needs of patients and families. Participants also discussed the important role of child life services during the pandemic and the unique and multifaceted contributions CCLSs made to support patients, families, other medical professionals, and communities. Recommendations for supporting children and families in medical environments moving forward are discussed in light of lessons learned during the pandemic., Competing Interests: Conflict of InterestThe authors declare no competing interests., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Recently, schools have focused on supportive (e.g., behavioral supports) rather than punitive (e.g., suspension) strategies to reduce school pushout among marginalized youth. We examined the association between suspension and discipline practices for students with intersecting identities (e.g., LGBT youth of color). We used teacher and student data from 1,091 schools that participated in the California School Climate and California Healthy Kids Surveys. Relative to White LGBT youth, LGBT youth of color were at higher risk of being suspended, and youth were differentially affected by punitive policies depending on their race, sexual orientation, and/or gender identity. While supportive strategies were associated with lower risk of suspension, punitive practices were associated with higher risk of suspension, especially for LGBT youth of color., (© 2022 Society for Research on Adolescence.)

Gay-Straight Alliances (GSA) and school policies focused on support for lesbian, gay, bisexual, transgender, and queer/questioning youth may reduce bias-based bullying and enhance social supports in schools. Using multivariate regression, we tested the relationship between youth reports of the presence of GSAs and LGBTQ-focused policies, independently and mutually, with experiences bullying and perceived support (n = 1,061). Youth reported higher classmate support in the presence of GSAs and higher teacher support in the presence of LGBTQ-focused policies; the presence of both GSAs and LGBTQ-focused policies was associated with less bullying and higher perceived classmate and teacher support. The findings indicate that GSAs and LGBTQ-focused policies are distinctly and mutually important for fostering safer and more supportive school climates for youth., (© 2019 Society for Research on Adolescence.)

Inclusive policies that attend to sexual orientation and gender identity (SOGI) are associated with more supportive school environments for lesbian, gay, bisexual, and transgender (LGBT) youth. We use the 2013-2015 California Healthy Kids Survey (n = 113,148) matched with principal reports of school policies from the 2014 California School Health Profiles to examine differential effects of SOGI-focused policies for LGB and transgender youth. SOGI-focused policies had a direct association with less truancy, and moderated the association between sexual orientation/gender identity and other school outcomes. SOGI-focused policies were associated with more positive experiences and perceptions of school climate for LGB youth and, to a lesser extent, transgender youth. Findings underscore the importance of inclusive policies, especially those that address the unique needs of transgender students., (Copyright © 2019. Published by Elsevier Ltd.)

The magnitude of gender identity-related disparities in school-based outcomes is unknown because of a lack of representative studies that include measures of gender identity. By utilizing a representative sample generalizable to a broader population, this study elucidates the size of gender identity-related disparities, independent of sexual orientation, in school experiences associated with school connectedness and perceptions of school climate. Additionally, the inclusion of and comparison to results of a large non-representative sample allows for more direct comparisons to previous studies of the school experiences of transgender youth. The analyses in this study primarily draw on a sample of 31,896 youth representative of the middle and high school population in California who participated in the 2013-2015 California Student Survey (a subsample of the California Healthy Kids Survey, which includes the largest known sample of transgender youth). Over half the sample identified their sex as female (51.3%), and 398 identified as transgender (1.0%). The sample was racially and ethnically diverse: 30.7% identified as multiracial, 33.0% as White, 11.1% as Asian, 7.4% as Black, and 52.9% as Hispanic. Findings from multilevel analyses show that relative to non-transgender youth, transgender youth were more likely to be truant from school, to experience victimization and bias-based bullying, and to report more negative perceptions of school climate, though did not differ in self-reported grades. The findings have implications for improving school policies and practices to create safer and more supportive school climates for all youth.

Purpose: The purpose of this study was to examine rates of substance use between transgender and nontransgender youth using a representative population-based sample and to examine mediating risk factors., Methods: A statewide cross-sectional sample of California middle and high schools collected between 2013 and 2015. This representative sample of students in California included 335 transgender and 31,737 nontransgender youth. Using multivariate linear and logistic regression, we assessed differences between transgender and nontransgender youth in substance use behaviors related to alcohol, cigarette, marijuana, other illicit drugs, polysubstance use, and heavy episodic drinking. Substance use was assessed with lifetime use, age of onset, and past 30-day use for alcohol, cigarettes, and marijuana. Past 30-day use was also assessed for other illicit drugs and polysubstance use. Models were adjusted for demographics and risk factors including victimization, depressive symptoms, and perceived risk of substance use., Results: The prevalence of substance use was 2.5-4 times higher for transgender youth compared with their nontransgender peers (depending on the substance). Transgender youth were also at greater risk for early age of onset and recent substance use than nontransgender youth. In addition, psychosocial risk factors related to victimization, depressive symptoms, and perceived risk of substance use partially mediated the relationship between gender identity and substance use., Conclusions: Using data from the first representative study of youth to include a measure of gender identity, we show that transgender youth are at heightened risk for substance use compared with nontransgender peers. Future research is needed to identify the structural and psychosocial mechanisms that drive these disparities., (Copyright © 2017 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: No representative population-based studies of youth in the United States exist on gender identity-related disparities in suicidal ideation or on factors that underlie this disparity. To address this, this study examined gender identity-related disparities in the prevalence of suicidal ideation; evaluated whether established psychosocial factors explained these disparities; and identified correlates of suicidal ideation among all youth and stratified by gender identity., Method: Data were derived from the 2013 to 2015 California Healthy Kids Survey (CHKS; N = 621,189) and a weighted subsample representative of the Californian student population (Biennial Statewide California Student Survey [CSS], N = 28,856)., Results: Prevalence of past 12-month self-reported suicidal ideation was nearly twice as high for transgender compared with non-transgender youth (33.73% versus 18.85%; χ 2  = 35.48, p < .001). In fully adjusted models within the representative sample, transgender youth had 2.99 higher odds (95% CI 2.25-3.98) of reporting past-year suicidal ideation compared with non-transgender youth. Among transgender youth, only depressive symptoms (adjusted odds ratio 5.44, 95% CI 1.81-16.38) and victimization (adjusted odds ratio 2.66, 95% CI 1.26-5.65) remained significantly associated with higher odds of suicidal ideation in fully adjusted models. In multiple mediation analyses, depression attenuated the association between gender identity and suicidal ideation by 17.95% and victimization by 14.71%., Conclusion: This study uses the first representative population-based sample of youth in the United States that includes a measurement of gender identity to report on gender identity-related disparities in suicidal ideation and to identify potential mechanisms underlying this disparity in a representative sample., (Copyright © 2017 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Active optical processes such as amplification and stimulated emission promise to play just as important a role in nanoscale optics as they have in mainstream modern optics. The ability of metallic nanostructures to enhance optical nonlinearities at the nanoscale has been shown for a number of nonlinear and active processes; however, one important process yet to be seen is optical parametric amplification. Here, we report the demonstration of surface plasmon-enhanced difference frequency generation by integration of a nonlinear optical medium, BaTiO3, in nanocrystalline form within a plasmonic nanocavity. These nanoengineered composite structures support resonances at pump, signal, and idler frequencies, providing large enhancements of the confined fields and efficient coupling of the wavelength-converted idler radiation to the far-field. This nanocomplex works as a nanoscale tunable infrared light source and paves the way for the design and fabrication of a surface plasmon-enhanced optical parametric amplifier.

Bullying is common in U.S. schools and is linked to emotional, behavioral, and academic risk for school-aged students. School policies and practices focused on sexual orientation and gender identity (SOGI) have been designed to reduce bullying and show promising results. Most studies have drawn from students' reports: We examined teachers' reports of bullying problems in their schools along with their assessments of school safety, combined with principals' reports of SOGI-focused policies and practices. Merging two independent sources of data from over 3000 teachers (California School Climate Survey) and nearly 100 school principals (School Health Profiles) at the school level, we used multi-level models to understand bullying problems in schools. Our results show that SOGI-focused policies reported by principals do not have a strong independent association with teachers' reports of bullying problems in their schools. However, in schools with more SOGI-focused policies, the association between teachers' assessments of school safety and bullying problems is stronger. Recent developments in education law and policy in the United States and their relevance for student well-being are discussed., (Copyright © 2015 Society for the Study of School Psychology. Published by Elsevier Ltd. All rights reserved.)

In a standing wave optical cavity, the coupling of cavity modes, for example, through a nonlinear medium, results in a rich variety of nonlinear dynamical phenomena, such as frequency pushing and pulling, mode-locking and pulsing, modal instabilities, even complex chaotic behavior. Metallic nanowires of finite length support a hierarchy of longitudinal surface plasmon modes with standing wave properties: the plasmonic analog of a Fabry-Pérot cavity. Here we show that positioning the nanowire within the gap of a plasmonic nanoantenna introduces a passive, hybridization-based coupling of the standing-wave nanowire plasmon modes with the antenna structure, mediating an interaction between the nanowire plasmon modes themselves. Frequency pushing and pulling, and the enhancement and suppression of specific plasmon modes, can be controlled and manipulated by nanoantenna position and shape.

Plasmonic nanostructures are of particular interest as substrates for the spectroscopic detection and identification of individual molecules. Single-molecule sensitivity Raman detection has been achieved by combining resonant molecular excitation with large electromagnetic field enhancements experienced by a molecule associated with an interparticle junction. Detection of molecules with extremely small Raman cross-sections (~10(-30) cm(2) sr(-1)), however, has remained elusive. Here we show that coherent anti-Stokes Raman spectroscopy (CARS), a nonlinear spectroscopy of great utility and potential for molecular sensing, can be used to obtain single-molecule detection sensitivity, by exploiting the unique light harvesting properties of plasmonic Fano resonances. The CARS signal is enhanced by ~11 orders of magnitude relative to spontaneous Raman scattering, enabling the detection of single molecules, which is verified using a statistically rigorous bi-analyte method. This approach combines unprecedented single-molecule spectral sensitivity with plasmonic substrates that can be fabricated using top-down lithographic strategies.

Metallic nanoparticles exhibiting plasmonic Fano resonances can provide large enhancements of their internal electric near field. Here we show that nanomatryoshkas, nanoparticles consisting of an Au core, an interstitial nanoscale SiO2 layer, and an Au shell layer, can selectively provide either a strong enhancement or a quenching of the spontaneous emission of fluorophores dispersed within their internal dielectric layer. This behavior can be understood by taking into account the near-field enhancement induced by the Fano resonance of the nanomatryoshka, which is responsible for enhanced absorption of the fluorophores incorporated into the nanocomplex. The combination of compact size and enhanced light emission with internal encapsulation of the fluorophores for increased biocompatibility suggests outstanding potential for this type of nanoparticle complex in biomedical applications.

This chapter explores how fatherhood prompts struggle and growth in the psychological, social, and economic changes associated with the transition to adulthood. Little is known about these connections, especially for disadvantaged Latino and White fathers who live in small and mid-sized American communities. We draw on eight in-depth focus groups with 48 fathers (27 Latino and 21 White) who have children in low-income schools in a small and mid-sized American community. These men face significant challenges in establishing themselves at work-a central task of both adulthood and fatherhood-and in balancing these demands alongside the strong expectation that they also be involved fathers. Involved fathering is key to understanding dynamics related to identity and meaning and to relationships with spouses and friends, which are also intertwined with the process of becoming adult. The discussion considers how fatherhood can promote and constrain adult development for disadvantaged men., (© 2014 Wiley Periodicals, Inc.)

Previous evidence suggests soy genistein may be protective against prostate cancer, but whether this protection involves an estrogen receptor (ER)-dependent mechanism is unknown. To test the hypothesis that phytoestrogens may act through ERα or ERβ to play a protective role against prostate cancer, we bred transgenic mice lacking functional ERα or ERβ with transgenic adenocarcinoma of mouse prostate (TRAMP) mice. Dietary genistein reduced the incidence of cancer in ER wild-type (WT)/transgenic adenocarcinoma of mouse prostate mice but not in ERα knockout (KO) or ERβKO mice. Cancer incidence was 70% in ERWT mice fed the control diet compared with 47% in ERWT mice fed low-dose genistein (300 mg/kg) and 32% on the high-dose genistein (750 mg/kg). Surprisingly, genistein only affected the well differentiated carcinoma (WDC) incidence but had no effect on poorly differentiated carcinoma (PDC). No dietary effects have been observed in either of the ERKO animals. We observed a very strong genotypic influence on PDC incidence, a protective effect in ERαKO (only 5% developed PDC), compared with 19% in the ERWT, and an increase in the incidence of PDC in ERβKO mice to 41%. Interestingly, immunohistochemical analysis showed ERα expression changing from nonnuclear in WDC to nuclear in PDC, with little change in ERβ location or expression. In conclusion, genistein is able to inhibit WDC in the presence of both ERs, but the effect of estrogen signaling on PDC is dominant over any dietary treatment, suggesting that improved differential targeting of ERα vs. ERβ would result in prevention of advanced prostate cancer.

Au nanoparticles deposited on a metallic film act as nanoantenna receivers and transmitters for the coupling of free-space radiation into, and out of, 2D surface plasmons. Nanosteps, sub-10-nm gaps between metallic films of differing thickness, can also launch and detect surface plasmons. Here we use both types of structures to locally launch propagating surface plasmon waves and probe their properties. Nanoparticle-launched surface plasmons emerge as two lobes of nominally 90 degree angular width, propagating along the direction of incident polarization. Alternatively, plasmons can be launched unidirectionally, by asymmetric illumination of a nanoparticle receiver.

Background: A prostate cancer (PCa) biomarker with improved specificity relative to PSA is a public health priority. Hypermethylated DNA can be detected in body fluids from PCa patients and may be a useful biomarker, although clinical performance varies between studies. We investigated the performance of candidate PCa DNA methylation biomarkers identified through a genome-wide search., Methods: Real-time PCR was used to measure four DNA methylation biomarkers: GSTP1 and three previously unreported candidates associated with the genes RASSF2, HIST1H4K, and TFAP2E in sodium bisulfite-modified DNA. Matched plasma and urine collected prospectively from 142 patients referred for prostate biopsy and 50 young asymptomatic males were analyzed., Results: Analysis of all biomarkers in urine DNA significantly discriminated PCa from biopsy negative patients. The biomarkers discriminated PCa from biopsy negative patients with AUCs ranging from 0.64 for HIST1H4K (95% CI 0.55-0.72, P < 0.00001) to 0.69 for GSTP1 (95% CI 0.60-0.77, P < 0.00001). All biomarkers showed minimal correlation with PSA. Multivariate analysis did not yield a panel that significantly improved performance over that of single biomarkers. All biomarkers showed greater sensitivity for PCa in urine than in plasma DNA., Conclusions: Analysis of the biomarkers in urine DNA significantly discriminated PCa from biopsy negative patients. The biomarkers provided information independent of PSA and may warrant inclusion in nomograms for predicting prostate biopsy outcome. The biomarkers' PCa sensitivity was greater for urine than plasma DNA. The biomarker performances in urine DNA should next be validated in formal training and test studies.

While N(2) and CO have played central roles in developing models of electronic structure, and their interactions with transition metals have been widely investigated, the valence isoelectronic diatomic molecules EX (E = group 13 element, X = group 17 element) have yet to be isolated under ambient conditions, either as the "free" molecule or as a ligand in a simple metal complex. As part of a program designed to address this deficiency, together with wider issues of the chemistry of cationic systems [L(n)M(ER)](+) (E = B, Al, Ga; R = aryl, amido, halide), we have targeted complexes of the type [L(n)M(GaX)](+). Halide abstraction is shown to be a viable method for the generation of mononuclear cationic complexes containing gallium donor ligands. The ability to isolate tractable two-coordinate products, however, is strongly dependent on the steric and electronic properties of the metal/ligand fragment. In the case of complexes containing ancillary pi-acceptor ligands such as CO, cationic complexes can only be isolated as base-trapped adducts, even with bulky aryl substituents at gallium. Base-free gallylene species such as [Cp*Fe(CO)(2)(GaMes)](+) can be identified only in the vapor phase by electrospray mass spectrometry experiments. With bis(phosphine) donor sets at the metal, the more favorable steric/electronic environment allows for the isolation of two-coordinate ligand systems, even with halide substituents at gallium. Thus, [Cp*Fe(dppe)(GaI)](+)[BAr(f)(4)](-) (9) can be synthesized and shown crystallographically to feature a terminally bound GaI ligand; 9 represents the first experimental realization of a complex containing a valence isoelectronic group 13/group 17 analogue of CO and N(2). DFT calculations reveal a relatively weakly bound GaI ligand, which is confirmed experimentally by the reaction of 9 with CO to give [Cp*Fe(dppe)(CO)](+)[BAr(f)(4)](-). In the absence of such reagents, 9 is stable for weeks in fluorobenzene solution, presumably reflecting (i) effective steric shielding of the gallium center by the ancillary phosphine and Cp* ligands; (ii) a net cationic charge which retards the tendency toward dimerization found for putative charge neutral systems; and (iii) (albeit relatively minor) population of the LUMOs of the GaI molecule through pi overlap with the HOMO and HOMO-2 of the [Cp*Fe(dppe)](+) fragment.

The thermodynamic factors underlying the use of ferroceneboronic esters as electrochemical or colorimetric fluoride ion sensors have been investigated through the synthesis of a range of systematically related derivatives differing in the number/nature of the boronic ester substituents and in the nature of ancillary ligands. Thus, if the shift in electrochemical potential associated with the conversion of one (or more) boronic ester group(s) to anionic boronate(s) on fluoride binding is sufficient to allow oxidation of the resulting host/guest complex by dioxygen, colorimetric sensing is possible. In practice, while monofunctional systems of the type CpFe[eta(5)-C(5)H(4)B(OR)(2)] offer selectivity in fluoride binding, electrochemical shifts in chloroform solution are insufficient to allow for a colorimetric response. Two chemical modification strategies have been shown to be successful in realizing a colorimetric sensor: (i) the use of the more strongly electron-donating Cp(*) ancillary ligand (which shifts the oxidation potential of both the free receptor and the resulting fluoride adduct cathodically by ca. -400 mV) and (ii) receptors featuring two or more binding sites and consequently a larger fluoride-induced electrochemical shift. Thus, in the case of [eta(5)-C(5)H(4)B(OR)(2)](2)Fe [(OR)(2) = OC(H)PhC(H)PhO, 2(s)], the binding of 2 equiv of fluoride gives an electrochemical shift (in chloroform) of -960 mV (cf. -530 mV for the corresponding monofunctional analogue, 1(s)). Related tris- and tetrakis-functionalized systems are also shown to be oxidized as the bis(fluoride) adducts, presumably because of fast oxidation kinetics, relative to the rate of the (electrostatically unfavorable) binding of a third equivalent of fluoride. Furthermore, the rate of sensor response (as measured by UV/vis spectroscopy) is found to be strongly enhanced by the presence of pendant (uncomplexed) three-coordinate boronic ester functions (e.g., a rate enhancement of 1-2 orders of magnitude for 3(s)/4(s) with respect to 2(s)) and/or delocalized aromatic substituents.

Insertion reactions of dicyclohexylcarbodiimide with aminoboranes and with aminoboryl and -borylene transition metal complexes have been examined as potential routes to new boron-containing ligand systems. Reactions with systems containing two-coordinate boron centres are found to be significantly more facile than those with three-coordinate substrates. Thus, reaction of (dicyclohexylamino)boron dichloride () with dicyclohexylcarbodiimide over 36 h at 50 degrees C generates the (structurally authenticated) guanidinate complex Cy(2)NC(NCy)(2)BCl(2) () via insertion into the BN bond. By contrast, the corresponding reaction with the cationic aminoborylene complex [CpFe(CO)(2)(BNCy(2))](+)[BAr(f)(4)](-) () proceeds rapidly at ca.-30 degrees C, via initial insertion into the FeB bond to give [CpFe(CO)(2)C(NCy)(2)BNCy(2)](+)[BAr(f)(4)](-) (). Consistent with related studies, a key factor in facilitating such insertion chemistry is thought to be the formation of an initial donor/acceptor complex between the diimide and the group 13 centre. Thus, DFT studies suggest that [CpFe(CO)(2)B(NCy(2))(CyNCNCy)](+)[BAr(f)(4)](-) is a potential intermediate in the reaction of with CyNCNCy, and that further reaction to give the observed product, , is strongly exergic (-183 kJ mol(-1)). By contrast, DFT calculations for the alternative isomer [CpFe(CO)(2)B(CyN)(2)CNCy(2)](+)[BAr(f)(4)](-) (), formed by BN insertion, suggest that it is 112 kJ mol(-1) less stable than . Such experimental and computational findings imply that under reaction conditions where a suitable isomerisation pathway is available, cationic complexes such as , which contain a four-membered boron-donor heterocycle are likely to be disfavoured with respect to alternative C-bound isomers.

A simple, one-step synthesis of multinuclear Lewis acids can be driven with high selectivity towards either macrocyclic or polymeric arrays by appropriate choice of backbone framework.

A systematic investigation of fluoride anion binding properties as a function of chelate backbone has been carried out for ferrocene functionalised boronic esters of the types FcB(OR)2 and fc[B(OR)2]2 [Fc = ferrocenyl = (eta5-C5H5)Fe(eta5-C5H4); fc = ferrocendiyl = Fe(eta5-C5H4)2]. Cyclic boronic esters containing a saturated five- or six-membered chelate ring are readily synthesized from ferrocene, and selectively bind fluoride via Lewis acid/base chemistry in chloroform solution. The resulting complexes are characterized by relatively weak fluoride binding (e.g.K = 35.8 +/- 9.8 M(-1) for FcBO2C2H2Ph2-S,S), and by cathodic shifts in the ferrocene oxidation potential that form the basis for electrochemical or colorimetric fluoride detection. The fluoride selectivity of these systems is attributed to relatively weak Lewis acidity, resulting in weak F- binding, and essentially no binding of potentially competitive anions. By contrast, more elaborate Lewis acid frameworks based on calix[4]arene (calixH4), such as (FcB)2calix or fcB2calix, do not survive intact exposure to standard fluoride sources (e.g. [nBu4N]F.xH2O solutions in chloroform or acetonitrile). Instead B-O bond cleavage occurs yielding the parent calixarene; the differences between alkoxo- and aryloxo-functionalised derivatives can be rationalised, at least in part, by consideration of the differences in electron donating capabilities of RO- (R = alkyl, aryl).

The synthesis, spectroscopic and structural characterization of the aryloxy and amino functionalized chloroboryl complexes (eta(5)-C(5)R(5))Fe(CO)(2)B(OMes)Cl (R = H, 2a ; R = Me, 3a) and (eta(5)-C(5)H(5))Fe(CO)(2)B(N(i)Pr(2))Cl (7a) are reported. Compound 2ais shown to be a versatile substrate for further boron-centred substitution chemistry leading to the asymmetric boryl complexes (eta(5)-C(5)H(5))Fe(CO)(2)B(OMes)ER(n) [ER(n) = OC(6)H(4)(t)Bu-4, 2c; ER(n) = SPh, 2d] with retention of the metal-boron bond. The reactivities of 2a, 3a and 7a towards the halide abstraction agent Na[BAr(f)(4)] have also been examined, in order to investigate the potential for the generation of cationic heteroatom-stabilized terminal borylene complexes. The application of this methodology to the mesityloxy derivatives and gives rise to B-F containing products, presumably via fluoride abstraction from the [BAr(f)(4)](-) counter-ion. By contrast, amino-functionalized complex 7a is more amenable to this approach, and the thermally robust terminal aminoborylene complex [(eta(5)-C(5)H(5))Fe(CO)(2)B(N(i)Pr(2))][BAr(f)(4)] (9) can be isolated in ca. 50% yield. The reactivity of 9towards a range of nucleophilic and/or unsaturated reagents has been examined, with examples of addition, protonolysis and metathesis chemistries having been established.

We examined the effects on female CD-1 mice of fetal exposure to low doses of the drug diethylstilbestrol (DES) (0.1 microg/kg/day) and the insecticide methoxychlor (MXC) (10 microg/kg/day) as well as 1000-fold higher doses: 100 microg/kg/day DES and 10,000 microg/kg/day MXC. Pregnant females were administered these chemicals on gestation days 12-18. At 7-8 months of age, female offspring were ovariectomized and implanted for 7 days with a Silastic capsule containing estradiol. Relative to controls, females exposed to the 0.1 microg DES dose showed significantly heavier uteri, while females exposed to the 100 microg DES dose showed significantly lighter uteri. Females exposed prenatally to the 10 microg/kg dose of MXC had significantly heavier uteri relative to females exposed to the 10,000 microg/kg dose of MXC, but neither group differed significantly from controls. Liver weight for females exposed to both doses of DES was significantly greater than controls. Using a microarray approach to analyze DNA methylation, an increase in ribosomal DNA (rDNA) methylation was observed. Sequence data and Southern analysis indicate an increase in 18S rDNA and 45S pre-rDNA methylation in uterine samples exposed prenatally to low and high doses of DES. We thus found opposite effects of fetal exposure to a low and a high dose of DES on the uterine response to estradiol (inverted-U dose-response relationship). In contrast, there was a monotonic dose-response relationship found for prenatal DES exposure on both liver weight and ribosomal DNA hypermethylation.

In this study we examine the effect of the phytoestrogen genistein on DNA methylation. DNA methylation is thought to inhibit transcription of genes by regulating alterations in chromatin structure. Estrogenic compounds have been reported to regulate DNA methylation in a small number of studies. Additionally, phytoestrogens are believed to affect progression of some human diseases, such as estrogen-dependent cancers, osteoporosis and cardiovascular disease. Specifically, our working hypothesis is that certain soy phytoestrogens, such as genistein, may be involved in preventing the development of certain prostate and mammary cancers by maintaining a protective DNA methylation profile. The objective of the present study is to use mouse differential methylation hybridization (DMH) arrays to test for changes in the methylation status of the cytosine guanine dinucleotide (CpG) islands in the mouse genome by examining how these methylation patterns are affected by genistein. Male mice were fed a casein-based diet (control) or the same diet containing 300 mg genistein/kg according to one of four regimens: control diet for 4 wk, genistein diet for 4 wk, control diet for 2 wk followed by genistein diet for 2 wk and genistein diet for 2 wk followed by control diet for 2 wk. DNA from liver, brain and prostate were then screened with DMH arrays. Clones with methylation differences were sequenced and compared with known sequences. In conclusion, consumption of genistein diet was positively correlated with changes in prostate DNA methylation at CpG islands of specific mouse genes.

Dietary supplements containing concentrates of plant-derived estrogens are being increasingly used by consumers as alternatives for hormone replacement therapy, for treatment of menopausal symptoms, and as cancer preventives. The effect of dietary genistein on dimethylbenz[a]anthracene (DMBA)-induced mammary tumor development was investigated in wild-type (ER alpha WT) and estrogen receptor-alpha knockout (ER alpha KO) mice. ER alpha WT and ER alpha KO mice were fed a casein-based diet containing 0 or 1 g genistein/kg diet from weaning. Tumors were induced by oral administration of DMBA and subscapular implantation of medroxyprogesterone acetate. No tumors were observed in ER alpha KO mice. In ER alpha WT mice, dietary intake of genistein influenced tumor development, enhancing anaplasia of mammary cancer. Mice consuming genistein expressed malignant mammary adenocarcinoma, whereas benign adenomas were observed in mice fed the control diet. Dietary intake was also influenced by genistein, with ER alpha WT and ER alpha KO mice fed genistein consuming less food (p < 0.0001) and subsequently weighing less than mice fed the control diet (p < 0.0001). Significant differences in food intake by genotype were also observed (p = 0.0017), with ER alpha KO mice consuming less than ER alpha WT mice. Overall, this study found no protective effect of genistein on DMBA-induced mammary tumors in mice and suggests a potential adverse effect on tumor development when high levels of genistein are consumed.

We utilized the transgenic adenocarcinoma mouse prostate (TRAMP) model to study the formation of abnormal mitosis in malignant tumors of the prostate. The results presented here are focused on centrosome and centriole abnormalities and the implications for abnormal cell divisions, genomic instability, and apoptosis. Centrosomes are microtubule organizing organelles which assemble bipolar spindles in normal cells but can organize mono-, tri-, and multipolar mitoses in tumor cells, as shown here with histology and electron microscopy in TRAMP neoplastic tissue. These abnormalities will cause unequal distribution of chromosomes and can initiate imbalanced cell cycles in which checkpoints for cell cycle control are lost. Neoplastic tissue of the TRAMP model is also characterized by numerous apoptotic cells. This may be the result of multipolar mitoses related to aberrant centrosome formations. Our results also reveal that centrosomes at the poles in mitotic cancer cells contain more than the regular perpendicular pair of centrioles which indicates abnormal distribution of centrioles during separation to the mitotic poles. Abnormalities in the centriole-centrosome complex are also seen during interphase where the complex is either closely associated with the nucleus or loosely dispersed in the cytoplasm. An increase in centriole numbers is observed during interphase, which may be the result of increased centriole duplication. Alternatively, these centrioles may be derived from basal bodies that have accumulated in the cell's cytoplasm, after the loss of cell borders. The supernumerary centrioles may participate in the formation of abnormal mitoses during cell division. These results demonstrate multiple abnormalities in the centrosome-centriole complex during prostate cancer that result in abnormal mitoses and may lead to increases in genomic instability and/or apoptosis.

Spinal muscular atrophy (SMA) is a motor neuron disease caused by mutations in the telomeric copy of the survival motor neuron (SMN(T)) gene. Over 90% of SMA patients harbor a deletion of SMN(T), but relatively few base-pair mutations have been reported. We report here a novel G279C mutation with a G to T transversion on exon 7 (nucleotide position 868) of SMN(T). Another missense mutation has been reported recently on position 869. The fact that two mutations on the same codon both result in SMA suggest a functional significance of this amino acid within the SMN protein.