bluuebunny/crossref_metadata_2025 huggingface dataset:
Anthropological Relocations and the Limits of Design
Authors: Suchman Lucy
Published: September 2010

This article takes as a touchstone the concept of location as it has been articulated through anthropology's reflections on its history and positioning as a field, and in relation to shifting engagements with contemporary technoscientific, political, and ethical problems. A second touchstone is one specific anthropological relocation—that is, into worlds of professional technology design. With figures of location and design in play, I describe some perspicuous moments that proved both generative and problematic in my own experience of establishing terms of engagement between anthropology and design. Though design has been considered recently as a model for anthropology's future, I argue instead that it is best positioned as a problematic object for an anthropology of the contemporary. In writing about design's limits, my argument is that, like anthropology, design needs to acknowledge the specificities of its place, to locate itself as one (albeit multiple) figure and practice of transformation.
Fungal Protein Production: Design and Production of Chimeric Proteins
Authors: Punt Peter J. , Levasseur Anthony , Visser Hans , Wery Jan , Record Eric
Published: September 2010

For more than a century, filamentous fungi have been used for the production of a wide variety of endogenous enzymes of industrial interest. More recently, with the use of genetic engineering tools developed for these organisms, this use has expanded for the production of nonnative heterologous proteins. In this review, an overview is given of examples describing the production of a special class of these proteins, namely chimeric proteins. The production of two types of chimeric proteins have been explored: (a) proteins grafted for a specific substrate-binding domain and (b) fusion proteins containing two separate enzymatic activities. Various application areas for the use of these chimeric proteins are described.
Gene Regulation in Borrelia burgdorferi
Authors: Samuels D. Scott
Published: September 2010

Borrelia burgdorferi, the spirochete that causes Lyme disease, is maintained in nature via an enzootic cycle that comprises a tick vector and a vertebrate host. Transmission from the tick to the mammal, acquisition from the mammal back to the tick, and adaptation to the two disparate environments require sensing signals and responding by regulating programs of gene expression. The molecular mechanisms utilized to effect these lifestyle changes have begun to be elucidated and feature an alternative sigma factor cascade in which RpoN (σ54) and RpoS (σS) globally control the genes required for the different phases of the enzootic cycle. The RpoN-RpoS pathway is surprisingly complex, entailing Rrp2, an unusual enhancer-binding protein and two-component regulatory system response regulator activated by acetyl phosphate; BosR, an unorthodox DNA-binding protein; DsrABb, a small noncoding RNA; and Hfq and CsrA, two RNA-binding proteins. B. burgdorferi also has a c-di-GMP signaling system that regulates the tick side of the enzootic cycle and whose function is only beginning to be appreciated.
Kin Discrimination and Cooperation in Microbes
Authors: Strassmann Joan E. , Gilbert Owen M. , Queller David C.
Published: September 2010

Recognition of relatives is important in microbes because they perform many behaviors that have costs to the actor while benefiting neighbors. Microbes cooperate for nourishment, movement, virulence, iron acquisition, protection, quorum sensing, and production of multicellular biofilms or fruiting bodies. Helping others is evolutionarily favored if it benefits others who share genes for helping, as specified by kin selection theory. If microbes generally find themselves in clonal patches, then no special means of discrimination is necessary. Much real discrimination is actually of kinds, not kin, as in poison-antidote systems, such as bacteriocins, in which cells benefit their own kind by poisoning others, and in adhesion systems, in which cells of the same kind bind together. These behaviors can elevate kinship generally and make cooperation easier to evolve and maintain.
Regulation of Alternative Sigma Factor Use
Authors: Österberg Sofia , Peso-Santos Teresa del , Shingler Victoria
Published: September 2010

Alternative bacterial sigma factors bind the catalytic core RNA polymerase to confer promoter selectivity on the holoenzyme. The different holoenzymes are thus programmed to recognize the distinct promoter classes in the genome to allow coordinated activation of discrete sets of genes needed for adaptive responses. To form the holoenzymes, the different sigma factors must be available to compete for their common substrate (core RNA polymerase). This review highlights (a) the roles of antisigma factors in controlling the availability of alternative sigma factors and (b) the involvement of diverse regulatory molecules that promote the use of alternative sigma factors through subversion of the domineering housekeeping σ70. The latter include the nucleotide alarmone ppGpp and small proteins (DksA, Rsd, and Crl), which directly target the transcriptional machinery to mediate their effects.
Microeconometric Strategies for Dealing with Unobservables and Endogenous Variables in Recreation Demand Models
Authors: Moeltner Klaus , von Haefen Roger
Published: September 2010

The past decade has witnessed significant advances in the microeconometric analysis of recreation data. In this review, we focus on two areas in which these innovations have been especially prolific: accounting for unobserved preference heterogeneity and controlling for unobserved and possibly endogenous site characteristics, such as congestion. Failure to appropriately address these issues with the nonlinear models typically used in recreation demand analysis can severely bias parameter and welfare estimates. We consider these issues of widespread importance within and beyond recreation demand applications. We also expect these estimation challenges to become more ubiquitous as the field gradually moves toward region-wide, multisite applications in reaction to large-scale environmental changes.
Valuing Mortality Risk Reductions: Progress and Challenges
Authors: Cropper Maureen , Hammitt James K. , Robinson Lisa A.
Published: September 2010

The value of mortality risk reduction is an important component of the benefits of environmental policies. In recent years, the number, scope, and quality of valuation studies have increased dramatically. Revealed-preference studies of wage compensation for occupational risks, on which analysts have primarily relied, have benefited from improved data and statistical methods. Stated-preference research has improved methodologically and expanded dramatically. Studies are now available for several health conditions associated with environmental causes, and researchers have explored many issues concerning the validity of the estimates. With the growing numbers of both types of studies, several meta-analyses have become available that provide insight into the results of both methods. Challenges remain, including better understanding of the persistently smaller estimates from stated-preference than from wage-differential studies and of how valuation depends on the individual's age, health status, and characteristics of the illnesses most frequently associated with environmental causes.
The Fixed Point Method for Fuzzy Approximation of a Functional Equation Associated with Inner Product Spaces
Authors: Gordji M. Eshaghi , Khodaei H.
Published: September 2010

Th. M. Rassias (1984) proved that the norm defined over a real vector space X is induced by an inner product if and only if for a fixed integer n ≥ 2,   holds for all x1, …, xn ∈ X. The aim of this paper is to extend the applications of the fixed point alternative method to provide a fuzzy stability for the functional equation which is said to be a functional equation associated with inner product spaces.
On the Existence of Solutions for Impulsive Duffing Dynamic Equations on Time Scales with Dirichlet Boundary Conditions
Authors: Li Yongkun , Zhang Tianwei
Published: September 2010

By using critical point theory, some new sufficient conditions for the existence of solutions of impulsive Duffing dynamic equations on time scales with Dirichlet boundary conditions are obtained. Some examples are also given to illustrate our results.
Modified Hybrid Algorithm for a Family of Quasi-"Equation missing" -Asymptotically Nonexpansive Mappings
Authors: Xu Yongchun , Zhang Xin , Kang Jinlong , Su Yongfu
Published: September 2010

The purpose of this paper is to propose a modified hybrid projection algorithm and prove strong convergence theorems for a family of quasi-"Equation missing"-asymptotically nonexpansive mappings. The method of the proof is different from the original one. Our results improve and extend the corresponding results announced by Zhou et al. (2010), Kimura and Takahashi (2009), and some others.
Asymptotic Properties of a Hepatitis B Virus Infection Model with Time Delay
Authors: Tian Xiaohong , Xu Rui
Published: September 2010

A hepatitis B virus infection model with time delay is discussed. By analyzing the corresponding characteristic equations, the local stability of each of the feasible equilibria of the model is studied. By using comparison arguments, it is proved that if the basic reproduction ratio is less than unity, the infection‐free equilibrium is globally asymptotically stable. If the basic reproduction ratio is greater than unity, by means of an iteration technique, sufficient conditions are derived for the global asymptotic stability of the virus‐infected equilibrium. Numerical simulations are carried out to illustrate the
theoretical results.
Developmental Effects of Perfluorononanoic Acid in the Mouse Are Dependent on Peroxisome Proliferator-Activated Receptor-Alpha
Authors: Wolf Cynthia J. , Zehr Robert D. , Schmid Judy E. , Lau Christopher , Abbott Barbara D.
Published: September 2010

Perfluorononanoic acid (PFNA) is one of the perfluoroalkyl acids found in the environment and in tissues of humans and wildlife. Prenatal exposure to PFNA negatively impacts survival and development of mice and activates the mouse and human peroxisome proliferator-activated receptor-alpha (PPAR). In the current study, we used PPAR knockout (KO) and 129S1/SvlmJ wild-type (WT) mice to investigate the role of PPAR in mediating PFNA-inducedin vivoeffects. Pregnant KO and WT mice were dosed orally with water (vehicle control: 10 ml/kg), 0.83, 1.1, 1.5, or 2 mg/kg PFNA on gestational days (GDs) 1–18 (day of sperm plug = GD 0). Maternal weight gain, implantation, litter size, and pup weight at birth were unaffected in either strain. PFNA exposure reduced the number of live pups at birth and survival of offspring to weaning in the 1.1 and 2 mg/kg groups in WT. Eye opening was delayed (mean delay days) and pup weight at weaning was reduced in WT pups at 2 mg/kg. These developmental endpoints were not affected in the KO. Relative liver weight was increased in a dose-dependent manner in dams and pups of the WT strain at all dose levels but only slightly increased in the highest dose group in the KO strain. In summary, PFNA altered liver weight of dams and pups, pup survival, body weight, and development in the WT, while only inducing a slight increase in relative liver weight of dams and pups at 2 mg/kg in KO mice. These results suggest that PPAR is an essential mediator of PFNA-induced developmental toxicity in the mouse.
Hydronephrosis Resulting from Bilateral Ureteral Stenosis: A Late Complication of Polyoma BK Virus Cystitis?
Authors: Basara N. , Rasche F.-M. , Schwalenberg T. , Wickenhauser C. , Maier M. , Ivovic J. , Niederwieser D. , Lindner T. H.
Published: September 2010

We report here a case of acute lymphoblastic leukemia in remission presenting a late-onset bilateral hydronephrosis probably due to polyoma BK virus-induced proliferation of bladder endothelium on both ostii. The diagnosis was made virologically by BK virus Polymerase Chain Reaction (PCR) detection in the absence of any other bladder disease. Awareness of this late complication is necessary not only in patients after renal transplantation but also in patients after hematopoietic stem cell transplantation from matched unrelated donor.
Fabrication of ZnO and ZnO:Sb Nanoparticles for Gas Sensor Applications
Authors: Kashyout A. B. , Soliman H. M. A. , Shokry Hassan H. , Abousehly A. M.
Published: September 2010

ZnO and Sb‐doped ZnO nanoparticles were successfully prepared using sol‐gel technique. Different concentrations of triethanolamine (TEA) were utilized as the preparation procedure to act as complexing agent that enhances the doping probability of the formed Sb‐doped ZnO nanopowder. Thick films of the prepared nanopowders were fabricated with spinner coating. Morphological characteristics, phase structure, chemical composition, thermal stability, and optical properties of the prepared nanopowders were measured and analyzed. The average crystallite size of ZnO and ZnO:Sb powders ranged between 19–28 nm according to the XRD calculations and TEM observations. The gas sensitivity of the homemade devices based on Sb‐doped ZnO nanoparticles towards O2 and CO2 gases as a function of temperature was measured and compared with undoped ZnO films. The gas sensitivity of the films was greatly improved after doping with Sb and reached its maximum value of ~86% for O2 gas at 93:7 wt% of Zn:Sb.
Unexpected High Response Rate to Traditional Therapy after Dendritic Cell‐Based Vaccine in Advanced Melanoma: Update of Clinical Outcome and Subgroup Analysis
Authors: Ridolfi Laura , Petrini Massimiliano , Fiammenghi Laura , Granato Anna Maria , Ancarani Valentina , Pancisi Elena , Scarpi Emanuela , Guidoboni Massimo , Migliori Giuseppe , Sanna Stefano , Tauceri Francesca , Verdecchia Giorgio Maria , Riccobon Angela , Ridolfi Ruggero
Published: September 2010

We reviewed the clinical results of a dendritic cell‐based phase II clinical vaccine trial in stage IV melanoma and analyzed a patient subgroup treated with standard therapies after stopping vaccination. From 2003 to 2009, 24 metastatic melanoma patients were treated with mature dendritic cells pulsed with autologous tumor lysate and keyhole limpet hemocyanin and low‐dose interleukin‐2. Overall response (OR) to vaccination was 37.5% with a clinical benefit of 54.1%. All 14 responders showed delayed type hypersensitivity positivity. Median overall survival (OS) was 15 months (95% CI, 8–33). Eleven patients underwent other treatments (3 surgery, 2 biotherapy, 2 radiotherapy, 2 chemotherapy, and 4 biochemotherapy) after stopping vaccination. Of these, 2 patients had a complete response and 5 a partial response, with an OR of 63.6%. Median OS was 34 months (range 16–61). Our results suggest that therapeutic DC vaccination could favor clinical response in patients after more than one line of therapy.
Simulated Nanoscale Peeling Process of Monolayer Graphene Sheet: Effect of Edge Structure and Lifting Position
Authors: Sasaki Naruo , Okamoto Hideaki , Masuda Shingen , Miura Kouji , Itamura Noriaki
Published: September 2010

The nanoscale peeling of the graphene sheet on the graphite surface is numerically studied by molecular mechanics simulation. For center‐lifting case, the successive partial peelings of the graphene around the lifting center appear as discrete jumps in the force curve, which induce the arched deformation of the graphene sheet. For edge‐lifting case, marked atomic‐scale friction of the graphene sheet during the nanoscale peeling process is found. During the surface contact, the graphene sheet takes the atomic‐scale sliding motion. The period of the peeling force curve during the surface contact decreases to the lattice period of the graphite. During the line contact, the graphene sheet also takes the stick‐slip sliding motion. These findings indicate the possibility of not only the direct observation of the atomic‐scale friction of the graphene sheet at the tip/surface interface but also the identification of the lattice orientation and the edge structure of the graphene sheet.
Gene Expression Profiling in Wild-Type and PPAR-Null Mice Exposed to Perfluorooctane Sulfonate Reveals PPAR-Independent Effects
Authors: Rosen Mitchell B. , Schmid Judith R. , Corton J. Christopher , Zehr Robert D. , Das Kaberi P. , Abbott Barbara D. , Lau Christopher
Published: September 2010

Perfluorooctane sulfonate (PFOS) is a perfluoroalkyl acid (PFAA) and a persistent environmental contaminant found in the tissues of humans and wildlife. Although blood levels of PFOS have begun to decline, health concerns remain because of the long half-life of PFOS in humans. Like other PFAAs, such as, perfluorooctanoic acid (PFOA), PFOS is an activator of peroxisome proliferator-activated receptor-alpha (PPAR) and exhibits hepatocarcinogenic potential in rodents. PFOS is also a developmental toxicant in rodents where, unlike PFOA, its mode of action is independent of PPAR. Wild-type (WT) and PPAR-null (Null) mice were dosed with 0, 3, or 10 mg/kg/day PFOS for 7 days. Animals were euthanized, livers weighed, and liver samples collected for histology and preparation of total RNA. Gene profiling was conducted using Affymetrix 430_2 microarrays. In WT mice, PFOS induced changes that were characteristic of PPAR transactivation including regulation of genes associated with lipid metabolism, peroxisome biogenesis, proteasome activation, and inflammation. PPAR-independent changes were indicated in both WT and Null mice by altered expression of genes related to lipid metabolism, inflammation, and xenobiotic metabolism. Such results are similar to studies done with PFOA and are consistent with modest activation of the constitutive androstane receptor (CAR), and possibly PPAR and/or PPAR/. Unique treatment-related effects were also found in Null mice including altered expression of genes associated with ribosome biogenesis, oxidative phosphorylation, and cholesterol biosynthesis. Of interest was up-regulation ofCyp7a1, a gene which is under the control of various transcription regulators. Hence, in addition to its ability to modestly activate PPAR, PFOS induces a variety of PPAR-independent effects as well.
Comparison of the Nasal Olfactory Organs of Various Species of Lizardfishes (Teleostei: Aulopiformes: Synodontidae) with Additional Remarks on the Brain
Authors: Fishelson L. , Golani D. , Galil B. , Goren M.
Published: September 2010

The olfactory organs of lizardfishes (Synodontidae) are situated in two capsules connected to the outside by incurrent and excurrent openings. The olfactory epithelium is in form of petal rosettes each composed of lamellae and a rephe, and bear olfactory receptor neurons, supporting cells and cells with kinocillia. The dimension of rosettes and lamellae, as well as the number of lamellae, increase with growth of the fish; until in adult fish these parameters remaine constant, species specific. In adultSynodusspp. andTrachinocephalus myopsthe rosettes are 3.5–4.0 mm long, with 5–8 lamellae, whereas inSauridaspp. they are 8.0 mm and possess up tp 22 lamellae. The number of ORN ranges from 2,600 on the smaller lamellae to 20,000 on the largest ones. The number of ORN/m of olfactory is ca. 30,000 inSauridaspp. Thus the rosettes ofS. macrolepiswith 20 lamellae possess a total of ca. 170,000 ORN, whereas those ofSy. variegatusandT. myopswith the average of six lamellae possess only ca. 50,000–65,000 ORN. The olfactory nerves lead from the rosettes to the olfactory balbs situated on the olfactory lobes. The differences among the species in olfactory organs are discussed in correlation with their distribution.
Condition Monitoring of Forward Curved Centrifugal Blower Using Coast Down Time Analysis
Authors: Rameshkumar G. R. , Rao B. V. A. , Ramachandran K. P.
Published: September 2010

Mechanical malfunctions such as, rotor unbalance and shaft misalignment are the most common causes of vibration in rotating machineries. Vibration is the most widely used parameter to monitor and asses the machine health condition. In this work, the Coast Down Time (CDT), which is an indicator of faults, is used to assess the condition of the rotating machine as a condition monitoring parameter. CDT is the total time taken by the system to dissipate the momentum acquired during sustained operation. Extensive experiments were conducted on Forward Curved Centrifugal Blower Test Rig at selected cutoff speeds for several combinations of combined horizontal and vertical parallel misalignment, combined parallel and angular misalignment, as well as for various unbalance conditions. As mechanical faults increase, a drastic decrease in CDT is found and this is represented as CDT reduction percentage. A specific correlation between the CDT reduction percentage, level of mechanical faults, and rotational cutoff speeds is observed. The results are analyzed and compared with vibration analysis for potential use of CDT as one of the condition monitoring parameter.
Defining Established and Emerging Microbial Risks in the Aquatic Environment: Current Knowledge, Implications, and Outlooks
Authors: Rowan Neil J.
Published: September 2010

This timely review primarily addresses important but presently undefined microbial risks to public health and to the natural environment. It specifically focuses on current knowledge, future outlooks and offers some potential alleviation strategies that may reduce or eliminate the risk of problematic microbes in their viable but nonculturable (VBNC) state andCryptosporidiumoocysts in the aquatic environment. As emphasis is placed on water quality, particularly surrounding efficacy of decontamination at the wastewater treatment plant level, this review also touches upon other related emerging issues, namely, the fate and potential ecotoxicological impact of untreated antibiotics and other pharmaceutically active compounds in water. Deciphering best published data has elucidated gaps between science and policy that will help stakeholders work towards the European Union's Water Framework Directive (2000/60/EC), which provides an ambitious legislative framework for water quality improvements within its region and seeks to restore all water bodies to “good ecological status” by 2015. Future effective risk-based assessment and management, post definition of the plethora of dynamic inter-related factors governing the occurrence, persistence and/or control of these presently undefined hazards in water will also demand exploiting and harnessing tangential advances in allied disciplines such as mathematical and computer modeling that will permit efficient data generation and transparent reporting to be undertaken by well-balanced consortia of stakeholders.
Bmi-1 Regulates Snail Expression and Promotes Metastasis Ability in Head and Neck Squamous Cancer-Derived ALDH1 Positive Cells
Authors: Yu Cheng-Chia , Lo Wen-Liang , Chen Yi-Wei , Huang Pin-I , Hsu Han-Shui , Tseng Ling-Ming , Hung Shih-Chieh , Kao Shou-Yen , Chang Charn-Jung , Chiou Shih Hwa
Published: September 2010

Recent studies suggest that ALDH1 is a putative marker for HNSCC-derived cancer stem cells. However, the regulation mechanisms that maintain the stemness and metastatic capability of HNSCC-ALDH1+cells remain unclear. Initially, HNSCC-ALDH1+cells from HNSCC patient showed cancer stemness properties, and high expression of Bmi1 and Snail. Functionally, tumorigenic properties of HNSCC-ALDH1+cells could be downregulated by knockdown of Bmi-1. Overexpression of Bmi-1 altered in expression propertyALDH1−cells to that ofALDH1+cells. Furthermore, knockdown of Bmi-1 enhanced the radiosensitivity of radiation-treated HNSCC-ALDH1+cells. Moreover, overexpression of Bmi-1 in HNSCC-ALDH1−cells increased tumor volume and number of pulmonary metastatic lesions by xenotransplant assay. Importantly, knock-down of Bmi1 in HNSCC-ALDH1+cells significantly decreased distant metastases in the lungs. Clinically, coexpression of Bmi-1/Snail/ALDH1 predicted the worst prognosis in HNSCC patients. Collectively, our data suggested that Bmi-1 plays a key role in regulating Snail expression and cancer stemness properties of HNSCC-ALDH1+cells.
Study of Mg Powder as Catalyst Carrier for the Carbon Nanotube Growth by CVD
Authors: Kang Jianli , Li Jiajun , Zhao Naiqin , Nash Philip , Shi Chunsheng , Sun Ronglu
Published: September 2010

The possibility of using magnesium powder as catalyst carrier for carbon nanotube growth by chemical vapor deposition, which may pave a new way to in situ fabricate CNT/Mg composites with high CNT dispersion, was investigated for the first time. The fabrication process of the catalyst supported on Mg powder involves the preparation of colloid by a deposition-precipitation method, followed by calcination and reduction. The results show that the interaction between catalyst and support plays an important role for the catalytic property of the catalyst. Ni alloyed with Mg shows no activity for the decomposition of methane. The introduction of Y in Ni/Mg catalyst can promote the reaction temperature between Ni and Mg and thus enhance the activity of the catalyst. A large amount of carbon nanotubes (CNTs) with an average diameter of 20 nm was obtained using Ni/Y/Mg catalyst at450∘C, while only a few short CNTs were obtained using Ni/Mg catalyst due to the low activity of the catalyst at lower temperature.
A Novel LAMA3 Mutation in a Newborn with Junctional Epidermolysis Bullosa Herlitz Type
Authors: Mazzucchelli Iolanda , Garofoli Francesca , Decembrino Lidia , Castiglia Daniele , Tadini Gianluca , Bellingeri Andrea , Borghesi Alessandro , Tzialla Chryssoula , Manzoni Paolo , Stronati Mauro
Published: September 2010

The case of a male neonate of 41 weeks’ gestation who developed blistering of the skin immediately after birth is described. His parents were consanguineous Tunisians. Electron microscopy of a cutaneous biopsy showed skin cleavage within the lamina lucida and immunoepitope mapping revealed a complete absence of laminin 332 expression. These findings referred to the diagnosis of junctional epidermolysis bullosa (JEB) Herlitz type. The neonate died at 3 months of age due to sepsis. Molecular analysis of laminin 332 chain genes LAMA3, LAMB3 and LAMC2 disclosed a novel homozygous nonsense mutation in LAMA3 (p.Y955X). Clinical and laboratory analyses are essential for the diagnosis of JEB subtypes, and molecular analysis screening is crucial to manage a new pregnancy in families with suspected cases of JEB.
Breast Milk-Transforming Growth Factor-β2 Specifically Attenuates IL-1β-Induced Inflammatory Responses in the Immature Human Intestine via an SMAD6- and ERK-Dependent Mechanism
Authors: Rautava Samuli , Nanthakumar N. Nanda , Dubert-Ferrandon Alix , Lu Lei , Rautava Jaana , Walker W. Allan
Published: September 2010

Background: Breast milk is known to protect the infant against infectious and immuno-inflammatory diseases, but the mechanisms of this protection are poorly understood. Objectives: We hypothesized that transforming growth factor-β2 (TGF-β2), an immunoregulatory cytokine abundant in breast milk, may have a direct anti-inflammatory effect on immature human intestinal epithelial cells (IECs). Methods: Human fetal ileal organ culture, primary human fetal IECs, and the human fetal small intestinal epithelial cell line H4 were stimulated with interleukin 1β (IL-1β) with or without TGF-β2. Pro-inflammatory cytokine secretion and mRNA expression were measured by ELISA and quantitative real-time polymerase chain reaction, respectively. Alterations in ERK signalling were detected from IECs by immunoblotting and in fetal ileal tissue culture by immunohistochemistry. SMAD6 knockdown was performed by transfecting the cells with SMAD6 siRNA. Results: TGF-β2 significantly attenuated IL-1β-induced pro-inflammatory cytokine production in fetal intestinal organ culture and the cell culture models. In addition, TGF-β2 reduced the IL-1β-induced IL-8 and IL-6 mRNA response in H4 cells. TGF-β2 markedly inhibited IL-1β-induced phosphorylation of ERK, which was necessary for the cytokine response. The inhibitory effect of TGF-β2 on IL-1β-induced cytokine production was completely abrogated by SMAD6 siRNA knockdown. Conclusions: TGF-β2 attenuates IL-1β-induced pro-inflammatory cytokine production in immature human IECs by inhibiting ERK signalling. The anti-inflammatory effect of TGF-β2 is dependent on SMAD6. Breast milk TGF-β2 may provide the neonate with important immunoregulatory support. TGF-β2 might provide a novel means to improve intestinal immunophysiology in premature neonates.
Hypoalbuminemia following Abdominal Surgery Leads to High Serum Unbound Bilirubin Concentrations in Newborns Soon after Birth
Authors: Miwa Akihiro , Morioka Ichiro , Hisamatsu Chieko , Fujioka Kazumichi , Morikawa Satoru , Shibata Akio , Yasufuku Masao , Yokoyama Naoki , Matsuo Masafumi
Published: September 2010

Background: The serum concentration of unbound bilirubin (UB), which is bilirubin not bound to albumin (Alb), is a better index than total bilirubin concentration (TB) for identifying infants at risk for developing bilirubin neurotoxicity. The degree to which the hypoalbuminemia following abdominal surgery in jaundiced newborns affects bilirubin binding is unknown. Objective: To determine whether lower Alb occurring in newborns undergoing abdominal surgery shortly after birth results in significantly higher UB in serum versus nonsurgical patients at comparable serum TB. Methods: A matched case-control study was conducted with term and late-preterm newborns. The surgery group included 15 newborns who underwent abdominal operation within 3 days after birth. Clinical and laboratory data (serum UB, TB, and Alb concentrations, UB/TB ratio, and binding constant) in the surgery group were collected and compared with those of 30 control newborns who did not undergo abdominal surgery (control group). Results: Serum UB and the UB/TB ratio in the surgery group were significantly higher than those in the control group (p < 0.02, p < 0.001, respectively), whereas there were no significant differences in serum TB and binding constant between the groups. Serum Alb concentrations in the surgery group were significantly lower than those in the control group (p < 0.001). When pre- and postoperative serum Alb concentrations were compared, there was a significant decrease from 3.4 to 2.7 g/dl (p < 0.001). Conclusions: Our study suggests that hypoalbuminemia following abdominal surgery causes a higher serum UB at comparable serum TB in newborns.
Intrauterine Growth Restriction Delays Feeding-Induced Gut Adaptation in Term Newborn Pigs
Authors: D’Inca Romain , Gras-Le Guen Christèle , Che Lianqiang , Sangild Per T. , Le Huërou-Luron Isabelle
Published: September 2010

Background: Neonates born after intrauterine growth restriction (IUGR) show higher mortality and morbidity and greater feeding problems postnatally. Objectives: We tested the hypothesis that IUGR affects the intestinal structure, function, microbiology and proinflammatory cytokine expression during the immediate neonatal period. Methods: We firstly compared organ weights and intestinal digestive enzyme activities between control and IUGR newborn piglets delivered by cesarean section at full term or prematurely (91% gestation). Next, we compared intestinal structure, function and microbiota in spontaneously delivered control and IUGR term piglets during the period 0–5 days of age, when intestinal adaptation is normally very rapid. Results: At the time of birth, organ weights and intestinal enzyme activities were not notably affected by IUGR, neither for preterm nor term pigs, except that IUGR was associated with a relatively long and thin intestine. Between birth and 5 days of age, the normal developmental pattern in the ileum and colon appeared to be delayed in term IUGR piglets, as indicated by lower ileal density (weight per unit length) and villous area (–20 to –30%), higher expression of the peptide transporter PEPT1 (+150% on day 2) and enhanced bacterial adhesion and translocation during days 2–5 (all p < 0.05). Further, expression of the proinflammatory cytokine IL-6 was modified in the intestine of term IUGR piglets at birth without any change in IL-1β. Conclusion: IUGR is associated with a longer and thinner intestine at birth, and during the immediate postnatal period, intestinal adaptation and bacterial colonization are altered in IUGR piglets born at full term.
Umbilical Incision Laparoscopic Surgery with One Assist Port for Anterior Resection
Authors: Kawahara Hidejiro , Watanabe Kazuhiro , Ushigome Takuro , Noaki Rohta , Kobayashi Susumu , Yanaga Katsuhiko
Published: September 2010

Background: A high surgical technique is required for laparoscopic anterior resection using single-incision laparoscopic surgery such as multiport surgery. We report a novel surgical technique of umbilical incision laparoscopic surgery with one assist port which could be performed like conventional multiport surgery. Methods: With the patient in the lithotomy position, a 3-cm longitudinal skin incision is made at the umbilicus and carried down to the peritoneum. A 12-mm and two 5-mm trocars are placed through the incision. Another 12-mm trocar is placed for the insertion of laparoscopic coagulation shears and a stapler in the right lower quadrant. After surgery, the trocar in the right lower quadrant is removed and a drain is replaced through the insertion site. The operator mainly uses two trocars, a 5-mm trocar placed at the umbilicus and a 12-mm trocar in the right lower quadrant, making it like conventional laparoscopic surgery. Results: The median operation time was 195 (range 180–205) min, intraoperative blood loss was 20 (range 0–60) ml, and none of the 3 patients had any complications postoperatively. Conclusion: As opposed to surgery with only three ports, so-called single-incision laparoscopic surgery, this operation can be performed much more comfortably if another port is inserted in the right lower quadrant.
Permeability Alterations after Surgical Trauma in Normal Rabbit Peritoneum
Authors: Kouritas V.K. , Tepetes K. , Christodoulides G. , Ioannou M. , Spyridakis M. , Gourgoulianis K.I. , Molyvdas P.A. , Hatzoglou C.H.
Published: September 2010

Background: To investigate whether surgical trauma in a rabbit adhesion formation model and the administration of normal saline (N/S), icodextrin (ID) and/or dimetindene maleate (DM) changes the permeability of the normal rabbit parietal peritoneum. Materials and Methods: A total of 45 female rabbits were operated on for adhesion formation and were euthanized 10 days later. In some rabbits, ID or N/S was instilled intraabdominally during operation, whereas in others DM was infused intravenously. In others, ID plus DM or no agent was used. Specimens were obtained postoperatively and were mounted between Ussing chambers. Amiloride was used to investigate Na+ channels. Transmesothelial resistance (RTM) was determined as a permeability indicator. Results: Amiloride increased the RTM of both surfaces. Surgical trauma increased RTM and partially inhibited the effect of amiloride. ID and N/S increased RTM and inhibited the effect of amiloride. Use of DM did not change RTM and did not inhibit the effect of amiloride. Use of ID plus DM slightly increased RTM, but the effect of amiloride was blocked. Conclusions: Surgical trauma impairs the permeability of the normal rabbit parietal peritoneum. ID or N/S surmounted this effect, but DM did not, suggesting that surgical trauma is a diffuse process. Antiadhesion measures influence peritoneal physiology.
Aquagenic Wrinkling of the Palms in an Adult Cystic Fibrosis Population
Authors: Tolland J.P. , Boyle J. , Hall V. , McKenna K.E. , Elborn J.S.
Published: September 2010

Background: Aquagenic wrinkling of the palms (AWP) is a rare condition characterised by the development of oedema and excessive wrinkling of the palms following exposure to water. It has frequently been associated with cystic fibrosis (CF). Early reports of AWP have only been case reports or small case series; there has only been one reported prevalence study of AWP in a CF population. Objective: To determine the incidence and characteristics of AWP in the adult CF population in Northern Ireland. Methods: 105 CF patients were interviewed. The patients were asked whether they noticed excess wrinkling of the hands when exposed to water. If they answered ‘yes’, further questions were asked regarding clinical characteristics. The atopic status, CF genotype and drug history were recorded for each patient. Formal testing of 7 patients was carried out. Results: Out of the 105 patients who were interviewed, 43 (41%) described AWP. Of the 43 patients with AWP, 20 were male and 23 were female. There was no association of AWP with genotype, atopy or concomitant drug intake. Conclusion: AWP appears to have an equal sex incidence, and the high number of cases in the population studied would suggest that this condition is underreported.
Gene Expression of FTO in Human Subcutaneous Adipose Tissue, Peripheral Blood Mononuclear Cells and Adipocyte Cell Line
Authors: Lappalainen Tiina , Kolehmainen Marjukka , Schwab Ursula , Pulkkinen Leena , de Mello Vanessa D.F. , Vaittinen Maija , Laaksonen David E. , Poutanen Kaisa , Uusitupa Matti , Gylling Helena
Published: September 2010

Background/Aims: The common polymorphism rs9939609 of the fat mass and obesity-associated gene (FTO) is strongly associated with obesity, but the biological function is still unknown. We compared the FTO gene expression in subcutaneous adipose tissue and peripheral blood mononuclear cells (PBMCs) between overweight and normal weight individuals. We also investigated if mRNA levels of FTO in adipose tissue correlated with the adiposity or inflammatory markers and mRNA levels of genes involved in the response to hypoxia (HIF-1a) and cell death(HMGB1). Results: The mRNA expression of FTO in adipose tissue was greater in obese than normal weight individuals (p < 0.001), but there was no difference in FTO expression in PBMCs. FTO mRNA levels did not correlate with adiposity or inflammatory markers and FTO expression was not influenced by the FTO rs9939609 genotype. FTO mRNA level correlated positively with gene expression levels of HIF-1a and HMGB1 in subcutaneous adipose tissue (r = 0.59, p < 0.001; r = 0.69, p < 0.001, respectively; adjusted for BMI and adipocyte cell size). Conclusions: Altogether, FTO expression appeared not to have a well-defined impact on clinical or biochemical parameters comprising the metabolic syndrome. The correlations with the genes related to hypoxia and cell death suggest novel biological activities for FTO.
Do Smooth Waters Run Deep? Alcohol Intoxication and the Effects of Water Consumption on Driving-Related Cognitions and Behavior
Authors: Spaanjaars N.L. , Spijkerman R. , Engels R.C.M.E.
Published: September 2010

The present study tested the effect of the combined use of alcohol and water on driving-related cognitions and behavior. Seventy-four female students performed a driving simulator task after having consumed alcohol or a placebo. Additionally, half of the participants consumed 0.5 liter of water. It was hypothesized that combining alcohol and water could lead to an underestimated perceived intoxication level resulting in more favorable driving cognitions and increased risk behavior. Our findings showed that the combined use of water and alcohol did not affect cognitions or behavior. Surprisingly, in the placebo condition, water intake increased risky driving cognitions and behavior in women with a history of accident involvement. Lacking a clear counterproductive effect when combined with alcohol, water could be a useful tool in limiting alcohol use among female drinkers.
Influence of Attention Deficit Hyperactivity Disorder and Conduct Disorder on Opioid Dependence Severity and Psychiatric Comorbidity in Chronic Methadone-Maintained Patients
Authors: Carpentier P.J. , van Gogh M.T. , Knapen L.J.M. , Buitelaar J.K. , De Jong C.A.J.
Published: September 2010

Background: Persistent attention deficit hyperactivity disorder (ADHD) and a history of conduct disorder (CD) are highly prevalent among patients with substance use disorders (SUD). We examined the influence of both diagnoses on problem severity, psychiatric comorbidity, and quality of life in methadone-maintained patients. Methods: 193 patients in long-term methadone maintenance treatment (MMT) were assessed for ADHD through a semi-structured interview. Psychiatric disorders and SUD were assessed with the MINI, the CIDI-SAM, and the SIDP-IV. Results: Childhood ADHD was diagnosed in 68 (35.2%) patients; 48 (24.9%) had persisting ADHD; a CD history was present in 116 (60.1%). Patients with adult ADHD had significantly higher problem severity scores, lower quality of life scores, more comorbid SUD and more psychiatric comorbidity. Although both ADHD and CD contributed to problem severity, addictive pathology and psychopathology, ADHD was found to substantially increase the risk of psychiatric comorbidity, independent of CD. Conclusion: ADHD in MMT patients is characterised by greater addiction severity and more comorbid psychopathology, only partly explained by the influence of a coexisting CD. The presence of ADHD in a substantial minority of patients accentuates the need for early detection and treatment of this complicating disorder.
Modulation of the Postischemic Immune Response to Improve Stroke Outcome
Authors: Becker Kyra J.
Published: September 2010

Recent advances in understanding how the poststroke immune response may contribute to ischemic brain injury are discussed in this article. In particular, the potential of modulating the postischemic immune response to improve stroke outcome is explored.
Rodent Models of Intracerebral Hemorrhage
Authors: MacLellan Crystal L. , Silasi Gergely , Auriat Angela M. , Colbourne Frederick
Published: September 2010

The collagenase and whole blood intracerebral hemorrhage (ICH) models are widely used to identify mechanisms of injury and to evaluate treatments. Despite preclinical successes, to date, no treatment tested in phase III clinical trials has benefited ICH patients. These failures call into question the predictive value of current ICH models. By highlighting differences between these common rodent models of ICH, we sought to help investigators choose the more appropriate model for their study and to encourage the use of both whenever possible. For instance, we previously reported substantial differences in the bleeding profile, progression of cell death, and functional outcome between these models. These and other differences influence the efficacy and mechanisms of action of various treatment modalities. Thus, in this review, we also summarize neuroprotective and rehabilitation findings in each model. We conclude that differences between ICH models along with our current inability to identify the more clinically predictive model necessitate that preclinical assessments should normally be done in both. Such an approach, coupled with better assessment practices, will likely improve chances of future clinical success.
Evaluating Strategies for the Treatment of Cerebral Cavernous Malformations
Authors: Li Dean Y. , Whitehead Kevin J.
Published: September 2010

Cerebral cavernous malformations are common vascular lesions of the central nervous system that predispose to seizures, focal neurological deficits, and potentially fatal hemorrhagic stroke. Human genetic studies have identified 3 genes associated with the disease, and biochemical studies of these proteins have identified interaction partners and possible signaling pathways. A recurring theme dominating the recent scientific literature is the causal link between mutations in the 3
cerebral cavernous malformation
genes and hyperactivation of the small GTP exchange protein, RhoA, and the efficacy of reducing this hyperactivation using inexpensive and well-studied medicines, statins. Familial cerebral cavernous malformation offers a unique opportunity to use a personalized genomic medicine approach to identify a subset of patients prone to intracerebal hemorrhage that may benefit from a pharmacological therapy, where presently only neurosurgical options are available.
Inflammatory Mechanisms of Stroke
Authors: Elkind Mitchell S.V.
Published: September 2010

Basic and clinical research provides evidence that inflammatory mechanisms play a central role in the pathogenesis and progression of atherosclerosis, plaque rupture, thrombosis, and stroke. Inflammatory biomarkers such as high-sensitivity C-reactive protein have been identified as predictors of first stroke and prognosis after stroke. The value of high-sensitivity C-reactive protein and other markers may depend on the characteristics of the study population; their utility may be less among populations with high vascular risk. A recent randomized, clinical trial suggests that the use of rosuvastatin therapy in otherwise healthy patients with high-sensitivity C-reactive protein >2 mg/dL can reduce the risk of a first stroke by 50%. The prognostic role of high-sensitivity C-reactive protein among patients after stroke, however, is less clear, and other biomarkers, including lipoprotein-associated phospholipase A
2
, may provide complementary information about the risk of stroke recurrence. Infections, moreover, may contribute to inflammation and stroke risk. Although no single infectious organism is likely to be identified as the direct cause of atherosclerosis, summary measures of multiple chronic infectious exposures, or “infectious burden,” have been associated with the risk of stroke and atherosclerosis affecting the carotid arteries. Acute infections have also been found to serve as stroke triggers in epidemiologic studies. Recommendations to vaccinate patients with cardiovascular disease against influenza represent the first specific anti-infective strategy to be used in vascular prophylaxis. Further studies are needed to determine the role of treatment of inflammation and infection in stroke prevention.
Endoluminal Scaffolds for Vascular Reconstruction and Exclusion of Aneurysms From the Cerebral Circulation
Authors: Lieber Baruch B. , Sadasivan Chander
Published: September 2010

The latest class of neuroendovascular devices being evaluated is intended to treat cerebral aneurysms. In addition to inducing flow stasis–mediated thrombosis of aneurysms and thus at times being referred to as flow diverters, these devices reconstitute pathologic arterial segments to near-physiologic normalcy. The successful implementation of such an endoluminal scaffold for vascular reconstruction in the cerebral circulation requires careful consideration of various factors drawn from engineering, physics, and biological sciences. Here we review some of these factors.
Neuroprotection in Subarachnoid Hemorrhage
Authors: Laskowitz Daniel T. , Kolls Brad J.
Published: September 2010

Despite advances in aneurysm ablation and the initial management of patients presenting with aneurysmal subarachnoid hemorrhage, delayed cerebral ischemia remains a significant source of morbidity. Traditionally, delayed cerebral ischemia was thought to be a result of vasospasm of the proximal intracranial vessels, and clinical trials have relied largely on radiographic evidence of vasospasm as a surrogate for functional outcome. However, a number of trials have demonstrated a dissociation between angiographic vasospasm and outcome, and more recent data suggest that other mechanisms of injury, such as microvascular dysfunction and complex neuronal-glial interactions, may influence the development of delayed ischemic deficit after aneurysmal subarachnoid hemorrhage. Our evolving understanding of the pathophysiology of delayed cerebral ischemia may offer the opportunity to test new therapeutic strategies in this area and improve clinical trial design.