bluuebunny/crossref_metadata_2025 huggingface dataset:
Notch Ligand Delta-Like 4 Regulates Development and Pathogenesis of Allergic Airway Responses by Modulating IL-2 Production and Th2 Immunity
Authors: Jang Sihyug , Schaller Matthew , Berlin Aaron A. , Lukacs Nicholas W.
Published: October 2010

Activation of the canonical Notch pathways has been implicated in Th cell differentiation, but the role of specific Notch ligands in Th2-mediated allergic airway responses has not been completely elucidated. In this study, we show that delta-like ligand 4 (Dll4) was upregulated on dendritic cells in response to cockroach allergen. Blocking Dll4 in vivo during either the primary or secondary response enhanced allergen-induced pathogenic consequences including airway hyperresponsiveness and mucus production via increased Th2 cytokines. In vitro assays demonstrated that Dll4 regulates IL-2 in T cells from established Th2 responses as well as during primary stimulation. Notably, Dll4 blockade during the primary, but not the secondary, response increased IL-2 levels in lung and lymph node of allergic mice. The in vivo neutralization of Dll4 was associated with increased expansion and decreased apoptosis during the primary allergen sensitization. Moreover, Dll4-mediated Notch activation of T cells during primary stimulation in vitro increased apoptosis during the contraction/resting phase of the response, which could be rescued by exogenous IL-2. Consistent with the role for Dll4-mediated IL-2 regulation in overall T cell function, the frequency of IL-4–producing cells was also significantly altered by Dll4 both in vivo and in vitro. These data demonstrate a regulatory role of Dll4 both in initial Th2 differentiation and in Th2 cytokine production in established allergic responses.
Polyinosinic-Polycytidylic Acid Treatment of Friend Retrovirus-Infected Mice Improves Functional Properties of Virus-Specific T Cells and Prevents Virus-Induced Disease
Authors: Gibbert Kathrin , Dietze Kirsten K. , Zelinskyy Gennadiy , Lang Karl S. , Barchet Winfried , Kirschning Carsten J. , Dittmer Ulf
Published: October 2010

The induction of type I IFN is the most immediate host response to viral infections. Type I IFN has a direct antiviral activity mediated by antiviral enzymes, but it also modulates the function of cells of the adaptive immune system. Many viruses can suppress type I IFN production, and in retroviral infections, the initial type I IFN is weak. Thus, one strategy of immunotherapy in viral infection is the exogenous induction of type I IFN during acute viral infection by TLR ligands. Along these lines, the TLR3/MDA5 ligand polyinosinic-polycytidylic acid [poly(I:C)] has already been used to treat viral infections. However, the immunological mechanisms underlying this successful therapy have not been defined until now. In this study, the Friend retrovirus (FV) mouse model was used to investigate the mode of action of poly(I:C) in antiretroviral immunotherapy. Postexposure, poly(I:C) treatment of FV-infected mice resulted in a significant reduction in viral loads and protection from virus-induced leukemia. This effect was IFN dependent because type I IFN receptor-deficient mice could not be protected by poly(I:C). The poly(I:C)-induced IFN response resulted in the expression of antiviral enzymes, which suppressed FV replication. Also, the virus-specific T cell response was augmented. Interestingly, it did not enhance the number of virus-specific CD4+ and CD8+ T cells, but rather the functional properties of these cells, such as cytokine production and cytotoxic activity. The results demonstrate a direct antiviral and immunomodulatory effect of poly(I:C) and, therefore, suggests its potential for clinical treatment of retroviral infections.
Dysregulation of Inflammatory Responses by Chronic Circadian Disruption
Authors: Castanon-Cervantes Oscar , Wu Mingwei , Ehlen J. Christopher , Paul Ketema , Gamble Karen L. , Johnson Russell L. , Besing Rachel C. , Menaker Michael , Gewirtz Andrew T. , Davidson Alec J.
Published: October 2010

Circadian rhythms modulate nearly every mammalian physiological process. Chronic disruption of circadian timing in shift work or during chronic jet lag in animal models leads to a higher risk of several pathologies. Many of these conditions in both shift workers and experimental models share the common risk factor of inflammation. In this study, we show that experimentally induced circadian disruption altered innate immune responses. Endotoxemic shock induced by LPS was magnified, leading to hypothermia and death after four consecutive weekly 6-h phase advances of the light/dark schedule, with 89% mortality compared with 21% in unshifted control mice. This may be due to a heightened release of proinflammatory cytokines in response to LPS treatment in shifted animals. Isolated peritoneal macrophages harvested from shifted mice exhibited a similarly heightened response to LPS in vitro, indicating that these cells are a target for jet lag. Sleep deprivation and stress are known to alter immune function and are potential mediators of the effects we describe. However, polysomnographic recording in mice exposed to the shifting schedule revealed no sleep loss, and stress measures were not altered in shifted mice. In contrast, we observed altered or abolished rhythms in the expression of clock genes in the central clock, liver, thymus, and peritoneal macrophages in mice after chronic jet lag. We conclude that circadian disruption, but not sleep loss or stress, are associated with jet lag-related dysregulation of the innate immune system. Such immune changes might be a common mechanism for the myriad negative health effects of shift work.
An Intrinsic Mechanism Predisposes Foxp3-Expressing Regulatory T Cells to Th2 Conversion In Vivo
Authors: Wang Yunqi , Souabni Abdallah , Flavell Richard A. , Wan Yisong Y.
Published: October 2010

Naturally occurring regulatory T (nTreg) cells express Foxp3 and were originally discovered as immune suppressors critical for self-tolerance and immune homeostasis. Through yet-to-be-defined mechanisms, nTreg cells were recently shown to convert into proinflammatory cells. Particularly, attenuation of Foxp3 expression led to Th2 conversion of nTreg cells in vivo. In this paper, we demonstrated an nTreg-specific mechanism controlling their Th2 conversion. We found that wild-type nTreg cells expressing reduced levels of Foxp3 but not those expressing no Foxp3 produced the Th2 cytokine IL-4. Intriguingly, IL-4 production by converted nTreg cells is required for Th2 differentiation of coexisting naive CD4 T cells in vivo, suggesting that Th2 conversion of nTreg cells might be critical for directing Th2 immune responses. Th2 conversion of nTreg cells was not due to their inability to become Th1 cells, because IFN-γ was produced by Foxp3-low–expressing cells when IL-4/STAT-6 signaling was abrogated. Surprisingly, however, unlike naive CD4 T cells whose IL-4 production is dependent on STAT-6, Foxp3-low–expressing cells generated IL-4 independent of STAT-6, indicating an intrinsic mechanism that favors nTreg-to-Th2 differentiation. Indeed, compared with naive CD4 T cells, nTreg expressed elevated levels of GATA-3 independent of STAT-6. And GATA-3 was required for nTreg-to-Th2 conversion. Foxp3 may account for this GATA-3 upregulation in nTreg cells, because ectopic expression of Foxp3 preferentially promoted GATA-3 but not T-bet expression. Thus, we have identified an intrinsic mechanism that imposes a Th2/Th1 imbalance and predisposes Foxp3-expressing cells to IL-4 production independent of STAT-6 signaling.
PTPα Activates Lyn and Fyn and Suppresses Hck to Negatively Regulate FcεRI-Dependent Mast Cell Activation and Allergic Responses
Authors: Samayawardhena Lionel A. , Pallen Catherine J.
Published: October 2010

Mast cell activation via FcεRI involves activation of the Src family kinases (SFKs) Lyn, Fyn, and Hck that positively or, in the case of Lyn, negatively regulate cellular responses. Little is known of upstream activators of these SFKs in FcεRI-dependent signaling. We investigated the role of receptor protein tyrosine phosphatase (PTP)α, a well-known activator of SFKs in diverse signaling systems, FcεRI-mediated mast cell activation, and IgE-dependent allergic responses in mice. PTPα−/− bone marrow-derived mast cells hyperdegranulate and exhibit increased cytokine and cysteinyl leukotriene secretion, and PTPα−/− mice display enhanced IgE-dependent anaphylaxis. At or proximal to FcεRI, PTPα−/− cells have reduced IgE-dependent activation of Lyn and Fyn, as well as reduced FcεRI and SHIP phosphorylation. In contrast, Hck and Syk activation is enhanced. Syk hyperactivation correlated with its increased phosphorylation at positive regulatory sites and defective phosphorylation at a negative regulatory site. Distal to FcεRI, we observed increased activation of PI3K and MAPK pathways. These findings demonstrate that PTPα activates the FcεRI-coupled kinases Lyn and Fyn and suppresses Hck activity. Furthermore, the findings indicate that hyperactivation of PTPα−/− mast cells and enhanced IgE-dependent allergic responses of PTPα−/− mice are due to the ablated function of PTPα as a critical regulator of Lyn negative signaling.
Slit2 Regulates Attractive Eosinophil and Repulsive Neutrophil Chemotaxis through Differential srGAP1 Expression during Lung Inflammation
Authors: Ye Bu-Qing , Geng Zhen H. , Ma Li , Geng Jian-Guo
Published: October 2010

Directional migration of leukocytes is an essential step in leukocyte trafficking during inflammatory responses. However, the molecular mechanisms governing directional chemotaxis of leukocytes remain poorly understood. The Slit family of guidance cues has been implicated for inhibition of leuocyte migration. We report that Clara cells in the bronchial epithelium secreted Slit2, whereas eosinophils and neutrophils expressed its cell-surface receptor, Robo1. Compared to neutrophils, eosinophils exhibited a significantly lower level of Slit-Robo GTPase-activating protein 1 (srGAP1), leading to activation of Cdc42, recruitment of PI3K to Robo1, enhancment of eotaxin-induced eosinophil chemotaxis, and exaggeration of allergic airway inflammation. Notably, OVA sensitization elicited a Slit2 gradient at so-called bronchus–alveoli axis, with a higher level of Slit2 in the bronchial epithelium and a lower level in the alveolar tissue. Aerosol administration of rSlit2 accelerated eosinophil infiltration, whereas i.v. administered Slit2 reduced eosinophil deposition. In contrast, Slit2 inactivated Cdc42 and suppressed stromal cell-derived factor-1α–induced chemotaxis of neutrophils for inhibiting endotoxin-induced lung inflammation, which were reversed by blockade of srGAP1 binding to Robo1. These results indicate that the newly identified Slit2 gradient at the bronchus–alveoli axis induces attractive PI3K signaling in eosinophils and repulsive srGAP1 signaling in neutrophils through differential srGAP1 expression during lung inflammation.
PRDM1/Blimp-1 Controls Effector Cytokine Production in Human NK Cells
Authors: Smith Matthew A. , Maurin Michelle , Cho Hyun Il , Becknell Brian , Freud Aharon G. , Yu Jianhua , Wei Sheng , Djeu Julie , Celis Esteban , Caligiuri Michael A. , Wright Kenneth L.
Published: October 2010

NK cells are major effectors of the innate immune response through cytolysis and bridge to the adaptive immune response through cytokine release. The mediators of activation are well studied; however, little is known about the mechanisms that restrain activation. In this report, we demonstrate that the transcriptional repressor PRDM1 (also known as Blimp-1 or PRDI-BF1) is a critical negative regulator of NK function. Three distinct PRDM1 isoforms are selectively induced in the CD56dim NK population in response to activation. PRDM1 coordinately suppresses the release of IFN-γ, TNF-α, and TNF-β through direct binding to multiple conserved regulatory regions. Ablation of PRDM1 expression leads to enhanced production of IFN-γ and TNF-α but does not alter cytotoxicity, whereas overexpression blocks cytokine production. PRDM1 response elements are defined at the IFNG and TNF loci. Collectively, these data demonstrate a key role for PRDM1 in the negative regulation of NK activation and position PRDM1 as a common regulator of the adaptive and innate immune response.
Hydroxylase Inhibition Abrogates TNF-α–Induced Intestinal Epithelial Damage by Hypoxia-Inducible Factor-1–Dependent Repression of FADD
Authors: Hindryckx Pieter , De Vos Martine , Jacques Peggy , Ferdinande Liesbeth , Peeters Harald , Olievier Kim , Bogaert Sara , Brinkman Brigitta , Vandenabeele Peter , Elewaut Dirk , Laukens Debby
Published: October 2010

Hydroxylase inhibitors stabilize hypoxia-inducible factor-1 (HIF-1), which has barrier-protective activity in the gut. Because the inflammatory cytokine TNF-α contributes to inflammatory bowel disease in part by compromising intestinal epithelial barrier integrity, hydroxylase inhibition may have beneficial effects in TNF-α–induced intestinal epithelial damage. The hydroxylase inhibitor dimethyloxalylglycin (DMOG) was tested in a murine model of TNF-α–driven chronic terminal ileitis. DMOG-treated mice experienced clinical benefit and showed clear attenuation of chronic intestinal inflammation compared with that of vehicle-treated littermates. Additional in vivo and in vitro experiments revealed that DMOG rapidly restored terminal ileal barrier function, at least in part through prevention of TNF-α–induced intestinal epithelial cell apoptosis. Subsequent transcriptional studies indicated that DMOG repressed Fas-associated death domain protein (FADD), a critical adaptor molecule in TNFR-1-mediated apoptosis, in an HIF-1α–dependent manner. Loss of this FADD repression by HIF-1α-targeting small interfering RNA significantly diminished the antiapoptotic action of DMOG. Additional molecular studies led to the discovery of a previously unappreciated HIF-1 binding site in the FADD promoter, which controls repression of FADD during hypoxia. As such, the results reported in this study allowed the identification of an innate mechanism that protects intestinal epithelial cells during (inflammatory) hypoxia, by direct modulation of death receptor signaling. Hydroxylase inhibition could represent a promising alternative treatment strategy for hypoxic inflammatory diseases, including inflammatory bowel disease.
Post Testicular Sperm Maturational Changes in the Bull: Important Role of the Epididymosomes and Prostasomes
Authors: Caballero Julieta , Frenette Gilles , Sullivan Robert
Published: October 2010

After spermatogenesis, testicular spermatozoa are not able to fertilize an oocyte, they must undergo sequential maturational processes. Part of these essential processes occurs during the transit of the spermatozoa through the male reproductive tract. Since the sperm become silent in terms of translation and transcription at the testicular level, all the maturational changes that take place on them are dependent on the interaction of spermatozoa with epididymal and accessory gland fluids. During the last decades, reproductive biotechnologies applied to bovine species have advanced significantly. The knowledge of the bull reproductive physiology is really important for the improvement of these techniques and the development of new ones. This paper focuses on the importance of the sperm interaction with the male reproductive fluids to acquire the fertilizing ability, with special attention to the role of the membranous vesicles present in those fluids and the recent mechanisms of protein acquisition during sperm maturation.
Optical remote sensing of the Gulf of Gabès – relation between turbidity, Secchi depth and total suspended matter
Authors: Katlane Essersi R. , Nechad B. , Ruddick K. , Zargouni F.
Published: October 2010

Abstract. Optical remote sensing is used here in the Gulf of Gabès to provide scientific information to support environmental management. The Gulf of Gabès is located in the southern east coast of Tunisia. It is a shallow continental shelf with semi-diurnal tides with average amplitude of 2 m. Industrial activities in this area since the early 1970s may have contributed to the degradation of the biodiversity of the ecosystem with eutrophication problems, and disappearance of benthic and planktonic species. To assess the long-term effect of anthropogenic and natural discharges on the Gulf of Gabès, turbidity and light penetration in the coastal waters is assessed from in situ measurements of total suspended matter concentration (TSM), Secchi depth and turbidity (TU) and from remote sensing data using a semi empirical algorithm to retrieve turbidity and total suspended matter products from moderate resolution imaging spectrometer MODIS Level 2 (L2) data.
Mechanical Ventilators in US Acute Care Hospitals
Authors: Rubinson Lewis , Vaughn Frances , Nelson Steve , Giordano Sam , Kallstrom Tom , Buckley Tim , Burney Tabinda , Hupert Nathaniel , Mutter Ryan , Handrigan Michael , Yeskey Kevin , Lurie Nicole , Branson Richard
Published: October 2010

Objective: The supply and distribution of mechanical ventilation capacity is of profound importance for planning for severe public health emergencies. However, the capability of US health systems to provide mechanical ventilation for children and adults remains poorly quantified. The objective of this study was to determine the quantity of adult and pediatric mechanical ventilators at US acute care hospitals.

Methods: A total of 5752 US acute care hospitals included in the 2007 American Hospital Association database were surveyed. We measured the quantities of mechanical ventilators and their features.

Results: Responding to the survey were 4305 (74.8%) hospitals, which accounted for 83.8% of US intensive care unit beds. Of the 52 118 full-feature mechanical ventilators owned by respondent hospitals, 24 204 (46.4%) are pediatric/neonatal capable. Accounting for nonrespondents, we estimate that there are 62 188 full-feature mechanical ventilators owned by US acute care hospitals. The median number of full-feature mechanical ventilators per 100 000 population for individual states is 19.7 (interquartile ratio 17.2–23.1), ranging from 11.9 to 77.6. The median number of pediatric-capable device full-feature mechanical ventilators per 100 000 population younger than 14 years old is 52.3 (interquartile ratio 43.1–63.9) and the range across states is 22.1 to 206.2. In addition, respondent hospitals reported owning 82 755 ventilators other than full-feature mechanical ventilators; we estimate that there are 98 738 devices other than full-feature ventilators at all of the US acute care hospitals.

Conclusions: The number of mechanical ventilators per US population exceeds those reported by other developed countries, but there is wide variation across states in the population-adjusted supply. There are considerably more pediatric-capable ventilators than there are for adults only on a population-adjusted basis.

(Disaster Med Public Health Preparedness. 2010;4:199-206)
Disaster Preparedness Among Families of Children With Special Health Care Needs
Authors: Baker Lisa R. , Baker Mark D.
Published: October 2010

Families with children with special health care needs may present a challenge for disaster responders. This study examined the level of personal disaster preparedness among this at-risk population in relation to the general population, and explores whether special health care needs or perception of disaster risk affects preparedness levels. A convenience sample of 145 families presenting to an urban tertiary care children's hospital was surveyed using a previously validated instrument to gather information on levels of preparedness and factors influencing preparedness. In spite of significant special health care needs and concern about disasters, families remain unprepared for a disaster event. Health care and psychosocial support workers are in a unique position to increase preparedness levels in this at-risk population.

(Disaster Med Public Health Preparedness. 2010;4:240-245)
Mesoporous Cage‐Like Silica Monoliths for Optical Sensing of Pollutant Ions
Authors: El‐Safty Sherif A. , Halada Kohmei , Yamada Hirohisa
Published: October 2010

An attractive means of improving pollution monitoring would be the use of simple, inexpensive, rapidly responsive and portable sensors. In this respect, selective optical sensing attracts much interest due to the use of ‘low‐tech’ spectroscopic instrumentation to detect relevant chemical species in biological and environmental processes. With recent advances in mesostructured materials and nanotechnologies, new methods are emerging to design optical sensors and biosensors and develop highly sensitive solid sensors. Recent developments have focused on tailoring specific sensors for the naked‐eye detection of highly toxic heavy metal ions such as lead, cadmium, antimony and mercury in aquatic samples. Sensitive, low‐cost, simple nanosensor designs have been successfully developed by the immobilization of hydrophobic and hydrophilic chromophore molecules into spherically nanosized cage cavities and surfaces. A rational strategy was crucial to the development of optical nanosensors that can be used to control the accurate recognition and signaling abilities of analyte species for ion‐sensing purposes. In this chapter, we report evidence of significant key factors in the development of receptors as ‘indicator dyes’ and surface‐confined materials as ‘carriers’ to broaden the applicability of optical chemical sensors for the selective discrimination of trace levels of toxic analytes. For the nanosensor design techniques described here, a dense pattern of immobilized hydrophobic ‘neutral’ and hydrophilic ‘charged’ chromophores with intrinsic mobility via extremely robust constructed sequences onto nanoscale structures was key to enhancing the sensing functionality of optical nanosensors. These nanosensor designs can be used as cage probe sinks with reliable control, for the first time, over the colorimetric recognition of highly toxic metal ions to low levels of ∼10
−9
 
M
. Control sensing assays were established to achieve enhanced signal response and color intensities. Moreover, these new classes of optical cage sensor exhibited long‐term stability of signaling and recognition functionalities that provided extraordinary sensitivity, selectivity, reusability and rapid kinetic detection and quantification of deleterious metal ions in the environment. This chapter details recent developments in the efficient design of optical nanosensors that employ mesoporous materials as model carriers to control the accurate recognition and signaling abilities of analyte species for ion‐sensing purposes.
Building Nonmagnetic Metal@Oxide and Bimetallic Nanostructures: Potential Applications in the Life Sciences
Authors: Mo Mao‐Song , Du Xu‐Sheng
Published: October 2010

Metallic nanostructures hold great potential for biomedical research such as biodetection and bioimaging, disease‐causing gene expression profiling, biodiagnostics, drug delivery and targeted therapeutics, and tissue engineering. A plethora of high‐quality metallic nanomotifs have been well developed to date. In this chapter we review the latest advances in the chemical build‐up of nonmagnetic metal@oxide and bimetallic nanostructures, as well as their current and future applications in the life sciences. Because of their unique size‐, shape‐ and composition‐dependent properties, the simultaneous detection of multiple signals with high stability, and dimensional similarities to biomacromolecules, nanostructured metals may be used to address key problems in the life sciences, from early cancer diagnostics to therapeutics.
Self‐Assembled pH‐Sensitive Nanoparticles: A Platform for Oral Delivery of Protein Drugs
Authors: Sonaje Kiran , Lin Kun‐Ju , Wang Jiun‐Jie , Mi Fwu‐Long , Chen Chiung‐Tong , Juang Jyuhn‐Huarng , Sung Hsing‐Wen
Published: October 2010

The oral route is considered to be the most convenient and comfortable means of drug administration for patients. Nevertheless, oral administration of hydrophilic macromolecules such as peptide/protein drugs is encountered with many difficulties. To overcome these difficulties, a pH‐sensitive nanoparticle (NP) carrier system, self‐assembled by chitosan (CS) and poly‐γ‐glutamic acid (γ‐PGA), is developed for paracellular transports of insulin. Oral administration of insulin‐loaded NPs shows a significant hypoglycemic action in diabetic rats and the corresponding relative bioavailability of insulin is approximately 15%. These findings suggest that the developed NP system is a promising carrier for improved transmucosal delivery of insulin in the small intestine. Besides insulin, this NP carrier system is expected to serve as a platform for oral delivery of hydrophilic macromolecules such as pharmaceutically active peptides/proteins, glycosaminoglycans, and oligonucleotides. Studies on the detailed mechanism of tight‐junction opening by CS or its derivatives are in progress, which is of paramount importance and needs to be established to aid further development in the use of NPs for oral delivery of hydrophilic macromolecules.
A General Approach for Patterning Multiple Types of Cells Using Holey PDMS Membranes and Microfluidic Channels
Authors: Yuan Bo , Li Yong , Wang Dong , Xie Yunyan , Liu Yingyi , Cui Li , Tu Fuquan , Li Hao , Ji Hang , Zhang Wei , Jiang Xingyu
Published: October 2010

A novel method combining microfluidic channels and holey poly(dimethylsiloxane) PDMS membranes is presented for patterning multiple types of cells on a large variety of substrate, including substrate bearing micro‐ and nanometer‐scale structures. Different kinds of cell are patterned on diverse flat substrates composed of various materials. Further, different cells are patterned on substrate with microgrooved substrate, and the influence of cell–cell and cell–substrate interactions about cell group behaviors is shown. This method provides a new approach for studying many processes in vitro caused by cell–cell and/or cell–substrate interactions. In addition, the method is straightforward, easy to access, convenient, and may be useful for a broad set of biological studies.
Statement on national worklife priorities
Authors: Cherniack Martin , Henning Rob , Merchant James A. , Punnett Laura , Sorensen Glorian R. , Wagner Gregory
Published: October 2010

The National Institute for Occupational Safety and Health (NIOSH) WorkLife Initiative (WLI) [http://www.cdc.gov/niosh/worklife] seeks to promote workplace programs, policies, and practices that result in healthier, more productive employees through a focus simultaneously on disease prevention, health promotion, and accommodations to age, family, and life stage. The Initiative incorporates the Institute's foundational commitment to workplaces free of recognized hazards into broader consideration of the factors that affect worker health and wellbeing. Workplace hazards, such as physical demands, chemical exposures, and work organization, often interact with non‐work factors such as family demands and health behaviors to increase health and safety risks. New workplace interventions being tested by the first three NIOSH WLI Centers of WorkLife Excellence are exploring innovative models for employee health programs to reduce the human, social, and economic costs of compromised health and quality of life. Many parties in industry, labor, and government share the goals of improving employee health while controlling health care costs. NIOSH convened a workshop in 2008 with representatives of the three Centers of Excellence to develop a comprehensive, long‐range strategy for advancing the WorkLife Initiative. The recommendations below fall into three areas: practice, research, and policy. Responding to these recommendations would permit the WorkLife Center system to establish a new infrastructure for workplace prevention programs by compiling and disseminating the innovative practices being developed and tested at the Centers, and elsewhere. The WLI would also extend the customary scope of NIOSH by engaging with multiple NIH Institutes that are already generating research‐to‐practice programs involving the working‐age population, in areas such as chronic disease prevention and management. Research to Practice (r2p) is a concept focused on the translation of research findings, technologies, and information into evidence‐based prevention practices and products that are adopted in the workplace or other “real‐world” settings. NIOSH's goal is to overcome the translational issues that now prevent state‐of‐the‐art occupational health, health promotion, and chronic disease research findings from benefiting working age populations immediately, regardless of workplace size, work sector, or region of the country. Am. J. Ind. Med. 54:10–20, 2011. © 2010 Wiley‐Liss, Inc.
Clues to an early diagnosis of Kallmann syndrome
Authors: Kaplan Julie D. , Bernstein Jonathan A. , Kwan Andrea , Hudgins Louanne
Published: October 2010

Kallmann syndrome (KS) is defined by the association of idiopathic hypogonadotropic hypogonadism and anosmia/hyposmia. Diagnosis is frequently delayed, however, because hypogonadotropic hypogonadism is usually not apparent until puberty and individuals with anosmia/hyposmia are often unaware of this sensory deficit. Mutations in at least six genes have been associated with KS; however, the sensitivity of molecular testing is only about 30% and, therefore, the diagnosis is largely based on clinical findings. We describe the findings in six individuals with KS, which demonstrate the utility of associated anomalies in making this diagnosis. Analysis of our case series and literature review suggests the consideration of KS for males with microphallus and/or cryptorchidism and for any patient with hearing loss, renal agenesis, and/or synkinesis. Conversely, patients with features of KS should have an audiology evaluation and a renal ultrasound. © 2010 Wiley‐Liss, Inc.
Discordance for Schimmelpenning–Feuerstein–Mims syndrome in monochorionic twins supports the concept of a postzygotic mutation
Authors: Rijntjes‐Jacobs Esther G.J. , Lopriore Enrico , Steggerda Sylke J. , Kant Sarina G. , Walther Frans J.
Published: October 2010

The Schimmelpenning–Feuerstein–Mims (SFM) syndrome comprises a craniofacial nevus sebaceus, seizures, developmental delay, ocular and skeletal abnormalities. It is a sporadic condition and hypothesized to result from mosaicism involving a lethal autosomal dominant gene. We report a second occurrence of discordant monozygotic (MZ) twins with severe SFM, supporting the concept of a postzygotic mutation. © 2010 Wiley‐Liss, Inc.
A novel X‐linked multiple congenital anomaly syndrome associated with an EBP mutation
Authors: Furtado Larissa V. , Bayrak‐Toydemir Pinar , Hulinsky Becki , Damjanovich Kristy , Carey John C. , Rope Alan F.
Published: October 2010

Mutations of the gene coding for emopamil binding protein (EBP) can lead to deficient activity of 3‐β‐hydroxysteroid Δ8, Δ7 isomerase and are most commonly identified in. association with the X‐linked dominant (male lethal) chondrodysplasia punctata (CDPX2), also known as Conradi‐Hunermann syndrome. Our group has identified a hemizygous EBP mutation in males with a phenotype remarkable for Dandy‐Walker malformation, cataracts, collodion skin and cryptorchidism. Additional findings of hydrocephalus, dysplasia of the corpus callosum, cardiovascular, craniofacial and skeletal anomalies were regularly seen in affected males and the family histories were supportive of an X‐linked ‐recessive condition. The regularly reproducible constellation of cardinal features aligns very nicely with other disorders of sterol biosynthesis and is further distinguished by an absence of arty clinical manifestations in obligate carrier females. Biochemical analysis of blood from cases demonstrated markedly increased levels of 8(9)‐cholestenol, and 8‐dehydroeholesterol and a mildly increased level of 7‐dehydrocholesterol; a similar pattern to what is seen in CDPX2. Sequence analysis of EJJP revealed a novel hemizygous missense mutation at position 141, predictive of a tryptophan to cysteine substitution (c.141G>T, p.W47C). The unaffected mothers were heterozygous for the c.141G>T mutation arid showed random X‐inactivation pattern upon. © 2010 Wiley‐Liss, Inc.
Fetal alcohol spectrum disorders: Extending the range of structural defects
Authors: Jones Kenneth Lyons , Hoyme H. Eugene , Robinson Luther K. , del Campo Miguel , Manning Melanie A. , Prewitt Lela M. , Chambers Christina D.
Published: October 2010

Although the structural phenotype of fetal alcohol syndrome (FAS) is established, prenatal exposure to alcohol may produce a broader spectrum of defects, fetal alcohol spectrum disorder (FASD). Documenting the full spectrum of defects associated with FASD is critical to determining the true incidence of this disorder. We examined 831 children from the Collaborative Initiative on Fetal Alcohol Spectrum Disorders using a structured protocol for diagnosis of FAS using the cardinal facial and growth features, and assessment of additional structural defects thought to occur more often in children with prenatal alcohol exposure. Subjects were classified as FAS, Deferred (some characteristic features of FAS), or No FAS, Groups were compared on prevalence of additional features and number of additional features observed, stratified by diagnostic category, sex, race, and age. Prevalence of most additional features was greatest among subjects with FAS and least among No FAS. A higher frequency of additional features was observed among FAS and Deferred subjects ≥12 years of age than among those under 12. FAS and Deferred Whites had greater frequency of additional features than Cape Colored. Prenatal alcohol exposure may produce a broad spectrum of structural defects that goes beyond FAS with implications regarding the impact of alcohol on the developing fetus, a prerequisite for ultimate prevention of FASD. © 2010 Wiley‐Liss, Inc.
Candidate gene sequencing of LHX2, HESX1, and SOX2 in a large schizencephaly cohort
Authors: Mellado Cecilia , Poduri Annapurna , Gleason Danielle , Elhosary Princess C. , Barry Brenda J. , Partlow Jennifer N. , Chang Bernard S. , Shaw Gary M. , Barkovich A. James , Walsh Christopher A.
Published: October 2010

Schizencephaly is a malformation of cortical development characterized by gray matter‐lined clefts in the cerebral cortex and a range of neurological presentations. In some cases, there are features of septo‐optic dysplasia concurrently with schizencephaly. The etiologies of both schizencephaly and septo‐optic dysplasia are thought to be heterogeneous, but there is evidence that at least some cases have genetic origin. We hypothesized that these disorders may be caused by mutations in three candidate genes: LHX2, a gene with an important cortical patterning role, and HESX1 and SOX2, genes that have been associated with septo‐optic dysplasia. We sequenced a large cohort of patients with schizencephaly, some with features of septo‐optic dysplasia, for mutations in these genes. No pathogenic mutations were observed, suggesting that other genes or non‐genetic factors influencing genes critical to brain development must be responsible for schizencephaly. © 2010 Wiley‐Liss, Inc.
Association of microtia with maternal obesity and periconceptional folic acid use
Authors: Ma Chen , Carmichael Suzan L. , Scheuerle Angela E. , Canfield Mark A. , Shaw Gary M.
Published: October 2010

The study objective was to examine the association of microtia with maternal intake of folic‐acid‐containing supplements and obesity. The study data included deliveries from 1997 to 2005 from the National Birth Defects Prevention Study. Non‐syndromic cases of microtia were compared to non‐malformed, population‐based liveborn control infants, by estimating adjusted odds ratios (AORs) and 95% confidence intervals (CIs) from logistic regression models that included maternal race/ethnicity, education, and study site. Maternal obesity was only weakly associated with microtia. Maternal periconceptional intake of folic‐acid‐containing vitamin supplements reduced the risk for microtia, but only among non‐obese women (OR: 0.63; 95% CI: 0.44–0.91). The reduced risk was stronger when analyses were restricted to isolated cases (OR: 0.51; 95% CI: 0.34–0.77), and it was independent of the level of maternal dietary folate intake. Adjusting for maternal race/ethnicity did not reveal alternative interpretations of this association. This analysis suggests that maternal periconceptional intake of folic‐acid‐containing supplements may provide protection from microtia for non‐obese women. © 2010 Wiley‐Liss, Inc.
Unilateral agenesis of the abdominal wall musculature: An early muscle deficiency
Authors: Gerard‐Blanluet Marion , Port‐Lis Marylin , Baumann Clarisse , Perrin‐Sabourin Laurence , Ebrad Patrick , Audry Georges , Delezoide Anne‐Lise , Verloes Alain
Published: October 2010

Prune‐belly sequence (PBS) usually results from early urethral obstruction. In rare cases, PBS seems to be due to a faulty primary development of the parietal mesenchyme leading to underdevelopment of the abdominal wall musculature, and disorganization of the smooth muscles in the urinary tract. We report on two patients with segmental, unilateral wall musculature deficiency associated with homolateral agenesis of ribs. One patient also had hemivertebrae and the other one ipsilateral diaphragmatic eventration and aplasia cutis. This combination of anomalies may represent a localized deficiency in the development of somitic mesoderm mesenchyme during early embryogenesis. © 2010 Wiley‐Liss, Inc.
Phenotype and natural history in Marshall–Smith syndrome
Authors: Shaw Adam C. , van Balkom Inge D.C. , Bauer Mislen , Cole Trevor R.P. , Delrue Marie‐Ange , Van Haeringen Arie , Holmberg Eva , Knight Samantha J.L. , Mortier Geert , Nampoothiri Sheela , Pušeljić Silvija , Zenker Martin , Cormier‐Daire Valerie , Hennekam Raoul C.M.
Published: October 2010

Marshall–Smith syndrome (MSS) is a distinctive entity of unknown etiology with fewer than 50 patients described in the medical literature to date. Through an International collaboration and use of an online wiki to facilitate data collection and sharing, we further delineate the phenotype and natural history of this syndrome. We present 15 new patients, the oldest being 30 years, provide an update on four previously published cases, and compare all patients with other patients reported in literature. Main clinical features are moderate to severe developmental delay with absent or limited speech, unusual behavior, dysharmonic bone maturation, respiratory compromise secondary to upper airway obstruction, short stature, and kyphoscoliosis. Facial features are characteristic with high forehead, underdeveloped midface, proptosis, anteverted nares, and everted lips. Minor abnormalities of brain morphology such as hypoplasia of the corpus callosum are common. Mortality from respiratory complications is high, but airway support increasingly allows survival into adulthood. Array‐CGH was performed on 12 of the cohort and no copy number variants of clear clinical relevance were identified. The present study is the first reported use of an online wiki to aid delineation of a genetic syndrome, and illustrates its value in collecting detailed data in rare conditions. © 2010 Wiley‐Liss, Inc.
Functional Materials: From Hard to Soft Porous Frameworks
Authors: Thomas Arne
Published: October 2010

This Review aims to give an overview of recent research in the area of porous, organic–inorganic and purely organic, functional materials. Possibilities for introducing organic groups that exhibit chemical and/or physical functions into porous materials will be described, with a focus on the incorporation of such functional groups as a supporting part of the pore walls. The number of organic groups in the network can be increased such that porous, purely organic materials are obtained.
FTIR equivalent weight determination of perfluorosulfonate polymers
Authors: Perusich Stephen A.
Published: October 2010

Fourier transform infrared (FTIR) and attenuated total reflectance (ATR) spectroscopy studies of the sulfonyl fluoride, potassium salt, and sulfonic acid forms of long and short side chain perfluorosulfonate polymers revealed bands indicative of the sidegroup and backbone compositions, endgroups on the main chain, water content, monomer concentration, and degree of salt hydrolysis. The equivalent weight (EW) of the polymer was obtained by titration and NMR measurements which were then calibrated to either the CF/COC absorbance band ratio for thin (<1.1 mil) films or to a CF/SO2F absorbance band ratio for thick films (5 to 25 mils). An FTIR measurement of the film thickness based on the CF group concentration was found to be both a function of the actual thickness and the EW; a method for compensating for this EW dependence is described. Esterification and fluorination of the polymers yielded FTIR measurements of the endgroup compositions on the polymer backbone which were shown to consist of COF, COOH, CO2CH3, and CFCF2 groups. Thermogravimetric Analysis Infrared (TGA‐IR) spectroscopy of the acid form polymers indicates that degradation begins by the decomposition of the SO3H group at 320°C followed by bulk deterioration above 400°C. The FTIR techniques detailed herein have been developed for accurate, reproducible, and rapid compositional measurements of Nafion® and other perfluorosulfonate polymers. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011
Synthesis and properties of novel fluorinated epoxy resins
Authors: Ge Z. Y. , Tao Z. Q. , Li G. , Ding J. P. , Fan L. , Yang S. Y.
Published: October 2010

A novel fluorinated epoxy compound, 4,4′‐bis(2,3‐epoxypropoxy‐phenyl)‐1‐(3‐trifluoromethylphenyl)‐2,2,2‐trifluoroethane (BEF), was synthesized starting from the coupling of phenol with 3′‐trifluoromethyl‐2,2,2‐trifluroacetophenone catalyzed by Lewis acid to yield an intermediate compound, which was then converted to the fluorinated epoxy by epoxidation with epichlorohydrin. BEF could be thermally cured with organic anhydride or aromatic amine as curing agents to produce thermally cured epoxy resins. Experimental results demonstrated that the thermally cured fluorinated epoxy resins showed good thermal stability with decomposition temperature at 5% weight loss of 342–364°C in nitrogen, high glass transition temperature (Tg) of 165–171°C (determined by DMA), and outstanding mechanical properties with flexural strengths of 79–119 MPa, flexural moduli of 2085–2130 MPa. The thermally cured fluorinated epoxy resins also exhibited excellent electric insulating properties with volume resistivity of 1.59–9.23 × 1016 Ω cm and surface resistivity of 4.81 × 1015–7.70 × 1016 Ω. The dielectric constants at 1 MHz were measured in the range of 3.1–3.4 and the dielectric dissipation factor (tan δ) in the range of 1.38–2.48 × 10−3. It was found that the fluorinated epoxy resins have improved electric insulating and dielectric properties as well as lower moisture adsorption compared with the corresponding commercial Bisphenol A type epoxy resins. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011
Wicking properties of various polyamide nanofibrous structures with an optimized method
Authors: De Schoenmaker Bert , Van der Schueren Lien , De Vrieze Sander , Westbroek Philippe , De Clerck Karen
Published: October 2010

In comparison with conventional structures, nanofibrous structures have unique characteristics, such as higher surface‐to‐volume ratios, smaller pores, and higher porosity. Their hydrophilic nature is a key characteristic for many applications. However, because of their high porosity, it is difficult to measure the hydrophilicity of nanofibrous structures with contact‐angle measurements. Therefore, characterization through wicking behavior is more appropriate. The International Organization for Standardization norm on wicking needs some refining to account for the specific nature of highly porous nanofibrous structures. A refined method was used on several structures that differed in the fiber diameter and the polyamide type. The structures with the thickest nanofibers had the highest wicking rates. At equilibrium, the wicking heights of structures of different polyamide types with the same average fiber diameter followed the trend expected from their intrinsic hydrophilicity. In the initial phase, the capillary forces established the wicking behavior. Later in the process, the wicking behavior was determined by the capillary forces and the hydrophilicity. In conclusion, the hydrophilicity of nanofibrous structures can be successfully determined by an optimized wicking procedure, and the fiber diameter is the dominant parameter for the resulting wicking height at equilibrium. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011
The illumination intensity and applied bias voltage on dielectric properties of au/polyvinyl alcohol (Co, Zn‐doped)/n‐Si Schottky barrier diodes
Authors: Uslu Habibe , Altındal Şemsettin , Tunç Tuncay , Uslu İbrahim , Mammadov Tofig S.
Published: October 2010

The Au/polyvinyl alcohol (PVA) (Co, Zn‐doped)/n‐Si Schottky barrier diodes (SBDs) were exposed to various illumination intensities. Illumination effect on the dielectric properties has been investigated by using capacitance–voltage (C–V) and conductance–voltage (G/ω–V) characteristics at 1 MHz and room temperature. The values of dielectric constant (ε′), dielectric loss (ε″), loss tangent (tanδ), electric modulus (M′ and M″), and AC electrical conductivity (σAC) were found strongly intensity dependent on both the illumination levels and applied bias voltage especially in depletion and accumulation regions. Such bias and illumination dependency of these parameters can be explained on the basis of Maxwell–Wagner interfacial polarization and restructuring and reordering of charges at interface states. In addition, the ε′–V plots also show an intersection feature at ∼ 2.8 V and such behavior of the ε′–V plots appears as an abnormality compared with the conventional behavior of an ideal SBD. The obtained results revealed that illumination intensity enhances the conductivity of Au/PVA(Co, Zn‐doped)/n‐Si SBD. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011
Synthesis, characterization, and application of polyethersulfone bound‐iminodiacetic acid
Authors: Cao Xue L. , Cheng Chong , Yin Ze H. , Bai Peng L. , Wei Qiang , Fang Bao H. , Zhao Chang S.
Published: October 2010

A new method to introduce iminodiacetic acid (IDA) onto polyethersulfone (PES) matrix through chlorosulfonation was described in this work, and the prepared PES‐IDA was used as adsorbent for the removal of metal ions from aqueous solutions. Chlorosulfonic groups (SO2Cl) were introduced onto PES first, then IDA was grafted onto PES by using the interactions between the chlorosulfonic group and the imino group of IDA. The grafted IDA was characterized by fourier transform infrared measurement, X‐ray photoelectron spectroscopy analysis, and thermogravimetric analysis spectra. The adsorbed amounts by the PES‐IDA for Cu2+ and Ag+ were 3.44 mg/g and 7.09 mg/g, respectively. The PES‐IDA adsorbent may expand the usage of PES in purification fields and could make some potential contributions to the polymer‐based adsorbents. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011
The preparation and characterization of crosslinked polytriazoles with different network grids
Authors: Wang Xiaofei , Wan Liqiang , E Yanpeng , Huang Farong , Du Lei
Published: October 2010

Crosslinked structures of a resin had a great influence on its properties. Studying the effect of a crosslinked network on resin properties will benefit to design and prepare a new resin with good performances. A series of alkyne group‐capped oligomers were designed and well characterized. The corresponding crosslinked polytriazoles with different network grids were obtained when multifunctional azide monomer was used as a crosslinking agent. The glass transition temperature (Tg) of the crosslinked polytriazoles was measured by Differential Scanning Calorimetry. The results showed networks with a small grid size would exihibit high Tgs. The relationship between Tg and the size of the network grids of the crosslinked polytriazoles was discussed. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011