bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulatory T Cell (Treg) Subsets Return in Patients with Refractory Lupus following Stem Cell Transplantation, and TGF-β-Producing CD8+ Treg Cells Are Associated with Immunological Remission of Lupus
Authors: Zhang Li , Bertucci Anne M. , Ramsey-Goldman Rosalind , Burt Richard K. , Datta Syamal K.
Published: October 2009

Compared with conventional drug therapy, autologous hemopoietic stem cell transplantation (HSCT) can induce very-long-term remission in refractory lupus patients. Herein, we show that in posttransplant patients, both CD4+CD25highFoxP3+ and an unusual CD8+FoxP3+ Treg subset return to levels seen in normal subjects; accompanied by almost complete inhibition of pathogenic T cell response to critical peptide autoepitopes from histones in nucleosomes, the major lupus autoantigen from apoptotic cells. In addition to a stably sustained elevation of FoxP3, posttransplant CD8 T cells also maintained markedly higher expression levels of latency-associated peptide (LAP), CD103, PD-1, PD-L1, and CTLA-4, as compared with pretransplant CD8 T cells that were identically treated by a one-time activation and rest in short-term culture. The posttransplant CD8 regulatory T cells (Treg) have autoantigen-specific and nonspecific suppressive activity, which is contact independent and predominantly TGF-β dependent. By contrast, the pretransplant CD8 T cells have helper activity, which is cell contact dependent. Although CD4+CD25high Treg cells return during clinical remission of conventional drug-treated lupus, the posttransplant patient’s CD8 Treg cells are considerably more potent, and they are absent in drug-treated patients in whom CD4 T cell autoreactivity to nucleosomal epitopes persists even during clinical remission. Therefore, unlike conventional drug therapy, hemopoietic stem cell transplantation generates a newly differentiated population of LAPhighCD103high CD8TGF-β Treg cells, which repairs the Treg deficiency in human lupus to maintain patients in true immunological remission.
FCRL3, an Autoimmune Susceptibility Gene, Has Inhibitory Potential on B-Cell Receptor-Mediated Signaling
Authors: Kochi Yuta , Myouzen Keiko , Yamada Ryo , Suzuki Akari , Kurosaki Tomohiro , Nakamura Yusuke , Yamamoto Kazuhiko
Published: October 2009

A polymorphism that up-regulates the expression of Fc receptor-like 3 (FCRL3) gene has recently been described as predisposing for several human autoimmune diseases. FCRL3 is preferentially expressed on B cells and is unique in displaying both an ITAM and an ITIM in the cytosolic domain, suggesting signaling functions. Herein, we show that FCRL3 potentially inhibits BCR-mediated signaling, using murine FcγRIIB/human FCRL3 chimeric protein. Coligation of the chimeric protein with BCR leads to phosphorylation of tyrosine residues in the cytosolic domain. This coligation inhibits cell tyrosine phosphorylation and calcium mobilization in addition to activation-induced cell death mediated by BCR signaling. Mutational analysis showed the tyrosine residues in two potential ITIMs at 662 and 692 offer the main contributions to this inhibition, which is further supported by strong associations of SH-2 domain-containing phosphatases with the following phosphotyrosine motifs: SHIP with the ITIM-like motif at 662; and SHP-1 and -2 with the canonical ITIM at 692. These results, together with previous genetic data, suggest that augmented inhibition of BCR-mediated signaling by FCRL3 with the disease-risk genotype alter the activation threshold and promote tolerance breakdown in B cells.
Fas Apoptosis Inhibitory Molecule Expression in B Cells Is Regulated through IRF4 in a Feed-Forward Mechanism
Authors: Kaku Hiroaki , Rothstein Thomas L.
Published: October 2009

Fas apoptosis inhibitory molecule (FAIM) was originally cloned as an inhibitor of Fas-mediated apoptosis in B cells that has been reported to affect multiple cell types. Recently, we found that FAIM enhances CD40L-mediated signal transduction, including induction of IFN regulatory factor (IRF)4, in vitro and augments plasma cell production in vivo. These results have keyed interest in the regulation of FAIM expression, about which little is known. Here, we show that Faim is regulated by IRF4. The Faim promoter contains three IRF binding sites, any two of which promote Faim expression. Faim promoter activity is lost following mutation of all three IRF binding sites, whereas activity of the full promoter is enhanced by concurrent expression of IRF4. In stimulated primary B cells, IRF4 expression precedes FAIM expression, IRF4 binds directly to the Faim promoter, and loss of IRF4 results in the failure of stimulated Faim up-regulation. Finally, FAIM is preferentially expressed in germinal center B cells. Taken together, these results indicate that FAIM expression is regulated through IRF4 and that this most likely occurs as part of germinal center formation. Because FAIM enhances CD40-induced IRF4 expression in B cells, these results suggest that induction of FAIM initiates a positive reinforcing (i.e., feed-forward) system in which IRF4 expression is both enhanced by FAIM and promotes FAIM expression.
Human Late Memory CD8+ T Cells Have a Distinct Cytokine Signature Characterized by CC Chemokine Production without IL-2 Production
Authors: Kim Tae Kon , St. John Lisa S. , Wieder Eric D. , Khalili Jahan , Ma Qing , Komanduri Krishna V.
Published: October 2009

Late memory T cell skewing is observed in the setting of immune recovery after cord blood transplantation, and may be associated with inferior control of viral reactivation and cancers. Therefore, we sought to understand how late memory cells differ functionally from earlier stage memory T cells, and whether surface phenotypes associated with differentiation stages were predictably associated with functional signatures. Higher order cytokine flow cytometry allows characterization of human T cells based on complex phenotypic markers and their differential capacity to simultaneously secrete effector proteins, including cytokines and chemokines. We used 8-color, 10-parameter cytokine flow cytometry to characterize the functional activation of human late memory CD8+ T cells defined by CD45RA and CD27 expression (CD27−CD45RA+). We assessed the 15 possible functional signatures of cells defined by production of IL-2, IFN-γ, TNF-α, and MIP-1β alone or in combination, following activation with Ags stimulating bypassing surface proteins (PMA:ionomycin) or through the TCR (e.g., viral Ags). Late memory CD8+ T cells produced abundant amounts of CC chemokines (MIP-1β, MIP-1α, and RANTES) but not IL-2. IL-2/IFN-γ coproduction, characteristic of protective immune responses to viral infections, was absent in late memory CD8+ T cells. These data demonstrate that functional cytokine signatures are predictably associated with CD8+ maturation stages, and that the polarization of late memory CD8+ T cells toward CC chemokine production and away from IL-2 production suggests a unique functional role for this subset.
On ℤ-Modules of Algebraic Integers
Authors: Bell J. P. , Hare K. G.
Published: October 2009

Abstract. Let q be an algebraic integer of degree d ≥ 2. Consider the rank of the multiplicative subgroup of ℂ* generated by the conjugates of q. We say q is of full rank if either the rank is d − 1 and q has norm ±1, or the rank is d. In this paper we study some properties of ℤ[q] where q is an algebraic integer of full rank. The special cases of when q is a Pisot number and when q is a Pisot-cyclotomic number are also studied. There are four main results.

(1)

If q is an algebraic integer of full rank and n is a fixed positive integer, then there are only finitely many m such that disc `ℤ[qm]´ = disc `ℤ[qn]´.

(2)

If q and r are algebraic integers of degree d of full rank and ℤ[qn] = ℤ[rn] for infinitely many n, then either q = ωr′ or q = Norm(r)2/dω/r′ , where r ′ is some conjugate of r and ω is some root of unity.

(3)

Let r be an algebraic integer of degree at most 3. Then there are at most 40 Pisot numbers q such that ℤ[q] = ℤ[r].

(4)

There are only finitely many Pisot-cyclotomic numbers of any fixed order.
Čebyšev Sets in Hyperspaces over Rn
Authors: Dawson and Robert J. MacG. , Moszyńska Maria
Published: October 2009

Abstract. A set in a metric space is called a Čebyšev set if it has a unique “nearest neighbour” to each point of the space. In this paper we generalize this notion, defining a set to be Čebyšev relative to another set if every point in the second set has a unique “nearest neighbour” in the first. We are interested in Čebyšev sets in some hyperspaces over Rn, endowed with the Hausdorff metric, mainly the hyperspaces of compact sets, compact convex sets, and strictly convex compact sets. We present some new classes of Čebyšev and relatively Čebyšev sets in various hyperspaces. In particular, we show that certain nested families of sets are Čebyšev. As these families are characterized purely in terms of containment,without reference to the semi-linear structure of the underlyingmetric space, their properties differ markedly from those of known Čebyšev sets.
Unit Elements in the Double Dual of a Subalgebra of the Fourier Algebra A(G)
Authors: Miao Tianxuan
Published: October 2009

Abstract.Let 𝒜 be a Banach algebra with a bounded right approximate identity and let ℬ be a closed ideal of 𝒜. We study the relationship between the right identities of the double duals ℬ** and 𝒜** under the Arens product. We show that every right identity of ℬ** can be extended to a right identity of 𝒜** in some sense. As a consequence, we answer a question of Lau and Ülger, showing that for the Fourier algebraA(G) of a locally compact groupG, an element ϕ ∈A(G)** is inA(G) if and only ifA(G)ϕ ⊆A(G) andEϕ = ϕ for all right identitiesEofA(G)**. We also prove some results about the topological centers of ℬ** and 𝒜**.
Subspaces of de Branges Spaces Generated by Majorants
Authors: Baranov Anton , Woracek Harald
Published: October 2009

For a given de Branges space ℋ (E ) we investigate de Branges subspaces defined in terms of majorants on the real axis. If ω is a nonnegative function on ℝ, we consider the subspace

We show that ℛω (E ) is a de Branges subspace and describe all subspaces of this form. Moreover, we give a criterion for the existence of positive minimal majorants.
First Countable Continua and Proper Forcing
Authors: Hart Joan E. , Kunen Kenneth
Published: October 2009

Assuming the Continuum Hypothesis, there is a compact, first countable, connected space of weight ℵ1 with no totally disconnected perfect subsets. Each such space, however, may be destroyed by some proper forcing order which does not add reals.
Characterization of Parallel Isometric Immersions of Space Forms into Space Forms in the Class of Isotropic Immersions
Authors: Maeda Sadahiro , Udagawa Seiichi
Published: October 2009

For an isotropic submanifold Mn (n ≧ 3) of a space form of constant sectional curvature c, we show that if the mean curvature vector of Mn is parallel and the sectional curvature K of Mn satisfies some inequality, then the second fundamental form of Mn in is parallel and our manifold Mn is a space form.
An Associative Model with Technological Base for the Competitiveness of Pymes: Case Colombian Florist
Authors: Lucia Giraldo Olga , Herrera Andrea
Published: October 2009

Globalization has opened markets where technology plays a key role in the search and achievement of competitiveness. This study, based on the cluster approach, first analyzes competitiveness of Colombian PyMes using diamond of Porter point of view, centered in florist sector; second it studies areas where information technologies would have higher impact; and third proposes associative solutions, based on the pattern of ASP, in order to provide PyMes access to world class technology managerial solutions at reasonable cost, increasing their efficiency, productivity and quality.
Risk Management Method to ERP Systems Implementation Based of Critical Sucess Factors
Authors: Rodrigues GambÃ´a Fernando Alexandre , Saez Caputo MÃ¡rcio , Bresciani Filho Ettore
Published: October 2009

From the second half of years 90, the Enterprise Resource Planning (ERP) systems implementation appears like one of the main investment focos related to the use of information technology in the companies, which aimed to acquire competitive advantages through cost reduction and differentiation of products with the use of these systems. ERP implementation showed to be much more than a technology project, involving structural and mannering changes, becoming a complex and high risk process for the organizations. In the literature specialized on ERP, there are many examples of the difficulties of this type of project and about implementations that had not reached the expected objectives, frustrating the expectations of the contractors. The present work describes, first of all, the development of a risk management method to ERP systems implementation, based on critical success factors. Then, a case of application of the considered method is analyzed, detailing the steps and the results gotten until the moment. To the end, evidences regarding to how the method helps to improve risk management during ERP implementations are presented.
Obelisco, Web Content Delivery
Authors: Valera Ramón
Published: October 2009

The basic principle for design and handling of any Website in the Internet or Intranet is centered in the attractiveness, easy to manage, up-to-date, reliability and accuracy. When they are administered by a person and the information generated in different levels of the organization surpasses their capacity, we find places outdated, inexact and not very coherent that can tunnel the image and credibility of a company in the world of the Internet. Due to this problem arises the necessity of creating a tool that automates the creation process, approval and distribution of the information, guaranteeing its coherence and presentation, using a simple and concrete process, this way OBELISCO emerges, as a tool based on APIs open code with friendly and simple interfaces that allows users with little or no experience in technology to place its works in the Web.
In search of dialogue and discourse in applied clinical informatics
Authors: Kim G. R. , Lehmann C. U.
Published: October 2009

We present a model of applied clinical informatics in the context of medical informatics in general, across the domain of health sciences and the continuum of information technology development and its adoption into workflow. The distinct challenges of applied clinical informatics present an opportunity to improve efforts through collaboration of the growing number of physicians, health institutional leaders and other health workers in successfully implementing working systems. This journal will be a forum for discussion regarding approaches to design, implement, deploy and evaluate systems and importantly, how to present experiences in a way to maximize sharing of those experiences.
Did you see the unicycling clown? Inattentional blindness while walking and talking on a cell phone
Authors: Hyman Ira E. , Boss S. Matthew , Wise Breanne M. , McKenzie Kira E. , Caggiano Jenna M.
Published: October 2009

We investigated the effects of divided attention during walking. Individuals were classified based on whether they were walking while talking on a cell phone, listening to an MP3 player, walking without any electronics or walking in a pair. In the first study, we found that cell phone users walked more slowly, changed directions more frequently, and were less likely to acknowledge other people than individuals in the other conditions. In the second study, we found that cell phone users were less likely to notice an unusual activity along their walking route (a unicycling clown). Cell phone usage may cause inattentional blindness even during a simple activity that should require few cognitive resources. Copyright © 2009 John Wiley & Sons, Ltd.
Passive vacuum solar flash desalination
Authors: Abutayeh Mohammad , Goswami D. Yogi
Published: October 2009

A model for a sustainable desalination process has been developed. The simulated process consists of pumping seawater through a solar heater before flashing it under a passively created vacuum in an elevated chamber. The vacuum enhances evaporation and is maintained by the balance between the hydrostatic pressure inside the elevated flash chamber and the atmospheric pressure. The developed model uses theoretical thermodynamic relations to describe the process setting it apart from previous empirical correlations. © 2009 American Institute of Chemical Engineers AIChE J, 2010
Progeroid syndrome with scleroderma‐like skin changes associated with homozygous R435C LMNA mutation
Authors: Madej‐Pilarczyk Agnieszka , Rosińska‐Borkowska Danuta , Rękawek Joanna , Marchel Michał , Szaluś Ewa , Jabłońska Stefania , Hausmanowa‐Petrusewicz Irena
Published: October 2009

Hutchinson–Gilford progeria is a rare genetic disorder resulting from mutations in the LMNA gene encoding lamin A/C. In addition to the classical phenotype usually caused by the 1824C>T mutation of LMNA, a number of atypical progeroid syndromes have been described. They have some distinct features, such as skeletal deformities or scleroderma‐like skin changes. The underlying defect is usually a homozygous mutation of LMNA, or a combined defect of LMNA and another gene, for example, ZMPSTE‐24. We present a 2‐year‐old girl born to consanguineous parents affected by progeroid syndrome with scleroderma‐like skin changes. Genetic analysis revealed the homozygous LMNA mutation 1303C>T (R435C). The same heterozygous mutation was found in the patient's parents and 11 other family members. The progeroid syndrome in our patient shares the signs of two laminopathies: progeria and restrictive dermatopathy. Two other children in the family died at the age of 2 due to a disease similar to that in the proposita. On the basis of the family pedigree we presume that these children probably had the same homozygous LMNA mutation. Scleroderma‐like skin changes in infants, associated with growth retardation and dysmorphic features, suggest premature aging syndrome, requiring genetic testing and counseling of asymptomatic carriers of LMNA mutations. © 2009 Wiley‐Liss, Inc.
Three novel mutations of the IRF6 gene with one associated with an unusual feature in Van der Woude syndrome
Authors: Yeetong Patra , Mahatumarat Charan , Siriwan Pichit , Rojvachiranonda Nond , Suphapeetiporn Kanya , Shotelersuk Vorasuk
Published: October 2009

Van der Woude syndrome (VWS) is a dominantly inherited disorder characterized by cleft lip with or without cleft palate and lip pits. It remains the most common syndromic form of oral clefts. Mutations in the interferon regulatory factor 6 (IRF6) gene have been identified in patients with VWS. We reported three unrelated families with lower lip anomalies. Two had lower lip pits, a cardinal sign of VWS, but the other had a heart‐shaped mass on lower lip without pits, oral clefts, or hypodontia. This isolated anomaly has not been previously observed in VWS. We performed mutation analysis by PCR‐sequencing the entire coding region of the IRF6 gene. Three potentially pathogenic mutations, c.145C>T (p.Q49X), c.171T>G (p.F57L), and 1306C>G (p.L436V) were successfully identified. All the missense mutations were not detected in 100 unaffected ethnic‐matched control chromosomes and have never been previously reported. The p.Q49X and p.F57L mutations were located in the highly conserved DNA binding domain while the p.L436V was located at the carboxy‐terminal region. This study reported an undescribed clinical feature of VWS and three novel mutations, expanding the phenotypic spectrum of VWS and mutational spectrum of IRF6. © 2009 Wiley‐Liss, Inc.
Molecular characterization of a monosomy 1p36 presenting as an Aicardi syndrome phenocopy
Authors: Bursztejn Anne‐Claire , Bronner Myriam , Peudenier Sylviane , Grégoire Marie‐José , Jonveaux Philippe , Nemos Christophe
Published: October 2009

Monosomy 1p36 is the most frequent terminal deletion known in Humans. Typical craniofacial features, developmental delay/mental retardation, seizures and sensorineural defects characterize 1p36 deletion syndrome. Aicardi syndrome (AIS) is a rare genetic disorder characterized by chorioretinal lacunae, corpus callosum agenesis and infantile spasms responsible for mental retardation. By screening DNA from diagnosed AIS patients with oligonucleotide array‐based comparative genomic hybridization (aCGH), we report a 1p36 monosomy in this study. There were no other deletions or duplications. Regarding clinical criteria, the patient did not have the typical facial appearance commonly described for 1p36 monosomy patients. We showed that this 1p36 monosomy corresponded to combined interstitial and terminal de novo deletions of the chromosome 1 leading to an 11.73 Mb deletion confirmed with qPCR. By microsatellite markers and FISH analyses, we have concluded that this deletion occurred on maternal chromosome 1 during oogenesis. We did find some clinical features shared by the 1p36 monosomy and AIS: infantile spasms, corpus callosum dysgenesis, ophthalmological abnormalities, and skeletal malformations. To date, no relationship between these two phenotypes has been established. We conclude that the monosomy 1p36 should be considered in the differential diagnosis of AIS. © 2009 Wiley‐Liss, Inc.
The development and evaluation of a survey to measure user engagement
Authors: O'Brien Heather L. , Toms Elaine G.
Published: October 2009

Facilitating engaging user experiences is essential in the design of interactive systems. To accomplish this, it is necessary to understand the composition of this construct and how to evaluate it. Building on previous work that posited a theory of engagement and identified a core set of attributes that operationalized this construct, we constructed and evaluated a multidimensional scale to measure user engagement. In this paper we describe the development of the scale, as well as two large‐scale studies (N=440 and N=802) that were undertaken to assess its reliability and validity in online shopping environments. In the first we used Reliability Analysis and Exploratory Factor Analysis to identify six attributes of engagement: Perceived Usability, Aesthetics, Focused Attention, Felt Involvement, Novelty, and Endurability. In the second we tested the validity of and relationships among those attributes using Structural Equation Modeling. The result of this research is a multidimensional scale that may be used to test the engagement of software applications. In addition, findings indicate that attributes of engagement are highly intertwined, a complex interplay of user‐system interaction variables. Notably, Perceived Usability played a mediating role in the relationship between Endurability and Novelty, Aesthetics, Felt Involvement, and Focused Attention.
Acoustic comfort in office buildings with double skin glass façades
Authors: Huckemann Volker , Leão Érika Borges , Leão Marlon
Published: October 2009

In the Project TwinSkin at the IGS Institut für Gebäude‐ und Solartechnik (Institute for Building Services and Energy Design) Brunswick/Germany, nine office buildings with double skin glass façades (DSF) were i.a. acoustically evaluated. Double skin façades (DSF), in comparison with other kind of façades, are frequently promoted to provide higher sound insulation from external noise, especially road traffic noise. DSF offer the advantage of operable windows or doors to the cavity, which provide occupant comfort; however, than questions about the impairment of acoustic comfort arise. The objective was to thoroughly analyse the apparent sound insulation properties of DSF in the extended frequency range from 50 to 5000 Hz. Measurements were performed according to the standard EN ISO 140‐5 for different operation conditions of the openings and single number quantities were calculated. Additionally their respective spectrum adaptation terms (C and Ctr) were considered. A remarkable influence of DSF design on the sound insulation properties was found. The results show high levels of weighted apparent sound reduction up to 60 dB, but also there were results from only 35 dB to 40 dB. Multi storey façades tend to better sound insulation performance in relation to the other types of DSF, an average of 13 dB higher values were found. Esthetical favourable arrangements of DSF can provide substantial negative influence on sound insulation.

Akustischer Komfort in Bürogebäuden mit Doppelglasfassaden.

In dem Projekt TwinSkin am IGS Institut für Gebäude‐ und Solartechnik Braunschweig wurden neun Bürogebäude mit Doppelglasfassaden (DGF) akustisch bewertet. Glasdoppelfassaden bieten gegenüber anderen Fassadenarten einen erhöhten Schutz der hinter der Fassade liegenden Räume vor von außen eindringendem Lärm, insbesondere Straßenverkehrslärm. Zudem können bei DSF Fenster oder Türen in den Fassadenzwischenraum geöffnet werden, was möglicherweise den Nutzerkomfort erhöht, aber Fragen über die Beeinträchtigung des akustischen Komforts entstehen lässt. Das Ziel der vorliegenden Arbeit war es, die vorhandene Schalldämmung von DSF im erweiterten Frequenzbereich von 50 bis 5000 Hz gründlich zu analysieren. Die Messungen wurden nach EN ISO 140‐5 für die verschiedenen Betriebsbedingungen der Öffnungen durchgeführt und es wurden Einzahlangaben berechnet. Zusätzlich wurden die jeweiligen Spektrum‐Anpassungswerte (C und Ctr) berücksichtigt. Es wurde ein bemerkenswerter Einfluss des DSF‐Designs auf die Schalldämmungseigenschaften gefunden. Die Ergebnisse zeigen ein hohes Schalldämm‐Maß bis zu 60 dB, aber es wurden auch Ergebnisse von nur 35 dB und 40 dB gemessen. Mehrgeschossige Fassaden weisen im Vergleich zu den anderen Arten von DSF eine bessere Schalldämmung auf, wobei im Durchschnitt 13 dB höhere Werte gefunden wurden. Ästhetisch bevorzugte Gestaltungen der DSF können dagegen einen erheblichen negativen Einfluss auf die Schalldämmung haben.
Indoor air quality defined by measurements and questionnaires in office buildings
Authors: Kuchen Ernesto , Fisch M. Norbert , Leão Marlon , Leão Érika Borges
Published: October 2009

The need for optimal ventilation of office spaces in Germany compels the designer to respect strict requirements on air quality as stated in the German Standard DIN EN 13779. In the present field work, an extensive survey is made in 270 work spaces belonging to 30 office buildings of various German cities, in which notable differences have been observed between the lineaments of the norm and the diagnosis issued by the users in regards to air quality. The purpose of the present work is to define the optimal concentration levels of carbon dioxide (CO2) on the basis of comparing the objective date obtained through measurements and the subjective data collected with a questionnaire responded to by the space users. The evaluation of the air quality level using the norm's criterion and the mean vote of users allows the determination of the percent value of users unsatisfied with the air quality in relation to the mean concentration levels of CO2. The research method consists of user inquiries, in the form of a short questionnaire, while making brief measurements on site with a mobile unit equipped with CO2 and TVOC (Total Volatile Organic Compounds) sensors. As the most relevant result it can be noted that, as long as the CO2 concentration levels do not rise above 1200 ppm, the users are incapable of discerning any decrease in air quality of the workspace. The minimum percentage of displeased users about air quality is about 30 %.

Luftqualität in Bürogebäuden auf Basis von Messungen und Nutzerbefragungen.

Zur Sicherstellung einer optimalen Lüftung von Arbeitsräumen ist der Planer in Deutschland zur Einhaltung der strengen Anforderungen an die Luftqualität aus DIN EN 13779 gezwungen. In der vorliegenden Arbeit wird vor Ort eine umfangreiche Untersuchung von 270 Arbeitsräumen in 30 Bürogebäuden durchgeführt. In Bezug auf die Luftqualität wurden zwischen der Richtlinie und dem Nutzerempfinden deutliche Unterschiede festgestellt. Der Zweck der Untersuchung ist die Definition der optimalen Konzentration von Kohlendioxid (CO2) auf Grund des Vergleichs zwischen objektiven Daten von Messungen und subjektiven Daten aus der Befragung der Nutzer von Arbeitsräumen. Die Bewertung der Luftqualität mit Hilfe der Norm und des mittleren Votums der Nutzer ermöglicht die Bestimmung der prozentualen Nutzerunzufriedenheit mit der Luftqualität in Abhängigkeit von den durchschnittlichen CO2‐Konzentrationen. Die Untersuchung besteht aus der Auswertung kurzer Fragebögen und Messungen mit einer mobilen Einheit, die mit CO2‐ und TVOC‐Sensoren (Total Volatile Organic Compounds) ausgestattet ist. Als wichtigstes Ergebnis kann festgestellt werden, dass solange die CO2‐Konzentration nicht über 1.200 ppm steigt, die Nutzer nicht in der Lage sind, eine Verringerung der Luftqualität in den Arbeitsräumen zu empfinden. Der geringste Anteil der auf Grund der Luftqualität unzufriedenen Nutzer liegt bei 30 %.
Antiproliferative and Proapoptotic Activities of a New Class of Pyrazole Derivatives in HL‐60 Cells
Authors: Anzaldi Maria , Macciò Chiara , Mazzei Mauro , Bertolotto Maria , Ottonello Luciano , Dallegri Franco , Balbi Alessandro
Published: October 2009

A series of N‐substituted pyrazole derivatives have been synthesized and tested for their anticancer effect on the HL‐60 leukaemia cell line. Four were active both in cell‐growth inhibition and in inducing apoptosis. The inhibition of cell growth mainly reflects a compound‐induced reduction in the number of cells in phases from S to M, whereas the induction of apoptosis involves inhibition of expression of Bcl‐2 and enhanced expression of Bax with consequent reduced activation of the proapoptotic caspase 3. Finally, preliminary experiments carried out with tumor cells from myelogenous leukaemic patients showed that the compounds 4c, 4l, 4m, and 4n are indeed capable of inducing apoptosis.
4,5,6‐Trisubstituted Piperidinones as Conformationally Restricted Ceramide Analogues: Synthesis and Evaluation as Inhibitors of Sphingosine and Ceramide Kinases and as NKT Cell‐Stimulatory Antigens
Authors: Mathew Thresen , Cavallari Marco , Billich Andreas , Bornancin Frederic , Nussbaumer Peter , De Libero Gennaro , Vasella Andrea
Published: October 2009

The conformationally based piperidinone sphingosine analogues 7, 8, 15, and 16 were synthesized from allylic alcohol 34 via lactams 31 and 32. The l‐arabino diol 7 and the l‐ribo diol 8 were transformed into the amino alcohols 17–24. The l‐gluco ceramide analogues 43, 46a, and 47, and the l‐altro ceramide analogues 51a and 52 were synthesized from either 31 or 32. The l‐ribo diols 8 and 16, and the amino alcohols 19 and 20 inhibit sphingosine kinase 1 (SPHK1), while the l‐arabino analogues 7, 15, 17, and 18 are inactive. The l‐arabino and the l‐ribo dimethylamines 21–24, the l‐gluco ceramide analogues 43, 46a, and 47, and the l‐altro ceramide analogues 51a and 52 did not block SPHK1. Neither the l‐arabino diol 7 nor the l‐ribo diol 8 inhibited SPHK2 or ceramide kinase. The l‐arabino diols 7 and 15 stimulate invariant natural killer T (iNKT) cells when presented by living antigen‐presenting cells (APC) and also by plate‐bound human CD1d, whereas the l‐ribo diols 8 and 16, the l‐arabino amino alcohols 17–18, and the dimethylamines 21–22 did not activate iNKT cells. The l‐gluco ceramide analogues 43, 46a, and 47 had strongly stimulatory effects on iNKT cells when presented by living APC and also by plate‐bound human CD1d, whereas the l‐altro ceramide analogue 52 activated only weakly. All activatory compounds induced preferentially the release of pro‐inflammatory cytokines, indicating the formation of a stable CD1dlipidT‐cell receptor complex.
The Biochemistry of Drug Metabolism – An Introduction
Authors: Krämer Stefanie D. , Testa Bernard
Published: October 2009

This review on intra‐individual factors affecting drug metabolism completes our series on the biochemistry of drug metabolism. The article presents the molecular mechanisms causing intra‐individual differences in enzyme expression and activity. They include enzyme induction by transcriptional activation and enzyme inhibition on the protein level. The influencing factors are of physiological, pathological, or external origin. Tissue characteristics and developmental age strongly influence enzyme‐expression patterns. Further influencing factors are pregnancy, disease, or biological rhythms. Xenobiotics, drugs, constituents of herbal remedies, food constituents, ethanol, and tobacco can all influence enzyme expression or activity and, hence, affect drug metabolism.
Ceramide induces endothelial cell senescence
Authors: Venable Mark E. , Yin Xinhe
Published: October 2009

Ceramide has been proposed to be a mediator of replicative senescence. Our aim was to determine whether ceramide induces senescence in vascular endothelial cells. Human umbilical vein endothelial cells were cultured to different population doubling levels and ceramide levels were quantitated. The endogenous levels of ceramide increased 2.4‐fold with senescence onset. Low passage cells were chronically treated with exogenous C6‐ceramide. This treatment induced a senescent phenotype as measured by an inhibition of cell proliferation and DNA replication while increasing senescence‐associated β‐galactosidase expression. This is the second cell type in which ceramide induces senescence, thus implicating ceramide as a general mediator of cellular senescence. Copyright © 2009 John Wiley & Sons, Ltd.
Simulation von Impulsversuchen mit BINSERT‐Mischern mittels Diskrete‐Elemente‐Methode
Authors: Weiler R. , Dau G. , Ripperger S.
Published: October 2009

Die Diskrete‐Elemente‐Methode (DEM) bietet die Möglichkeit, aufschlussreiche Informationen über die Vorgänge in fließenden Schüttgütern zu erlangen. Hierbei können z. B. Krafteinträge auf Silowände und ‐einbauten sowie Verweilzeitverteilungen berechnet werden. Damit bietet die DEM auch die Möglichkeit der Auslegung von Schwerkraftmischern. Im Folgenden wird die Modellierung von Impulsversuchen mit Mischsilos bzw. Schwerkraftmischern beschrieben, bei denen Verweilzeitverteilungen gewonnen werden. Es werden experimentelle und berechnete Ergebnisse präsentiert, die mit Mischsilos im Technikumsmaßstab ermittelt wurden. Die Ergebnisse zeigen, dass zwischen Messung und DEM‐Berechnung sowohl eine gute qualitative als auch quantitative Übereinstimmung erzielt wird.
High Value Products from Waste: Grape Pomace Extract—A Three‐in‐One Package for the Synthesis of Metal Nanoparticles
Authors: Baruwati Babita , Varma Rajender S
Published: October 2009

Metal nanoparticles of Au, Ag, Pd, and Pt have been synthesized in aqueous media using red grape pomace as a reducing agent and a capping agent. The particles are formed within a few seconds when exposed to microwave irradiation at a power level as low as 50 W. Particles could be formed at room temperature, but they tend to be amorphous in nature except for gold. A detailed study on the morphology of the ensuing particles with various reaction conditions has been carried out.
Comparative expression of zebrafish lats1 and lats2 and their implication in gastrulation movements
Authors: Chen Chun‐Hong , Sun Yong‐Hua , Pei De‐Sheng , Zhu Zuo‐Yan
Published: October 2009

Large tumor suppressor (Lats) is a Ser/Thr kinase, and it presents an important function in tumor suppression. lats was originally identified in Drosophila and recently in mammals. In mammals, it contains two homologues, lats1 and lats2. In the present study, lats1 and lats2 were characterized from zebrafish (Danio rerio), which is the first report of lats in a nonmammalian vertebrate. The primary structure, genomic organization, and phylogenesis of lats from different species were studied, and the results suggest that lats1 is the direct descendant of invertebrate lats, whereas lats2 is formed by genome duplication. In zebrafish, both lats genes are maternally expressed, while they show distinctly different expression profiles during gastrulation. lats1 is almost ubiquitously expressed through development, and lats2 is more prominently expressed in the non‐neural ectoderm region of zebrafish gastrula. Most intriguingly, as revealed by cell tracing and gene expression analysis, morpholino‐mediated knockdown of either lats1 or lats2 led to obvious defects of cell migration in gastrulation, indicating the functional significance of lats in gastrulation movements. Developmental Dynamics, 238:2850–2859, 2009. © 2009 Wiley‐Liss, Inc.
Mechanisms for split localization of Fgf10 expression in early lung development
Authors: Hirashima Tsuyoshi , Iwasa Yoh , Morishita Yoshihiro
Published: October 2009

In early lung development, epithelial tubes (lung buds) intrude into mesenchyme covered with pleural cells (lung border), and form tree‐like networks, by means of repeated use of morphogenetic processes: “elongation,” “terminal bifurcation,” and “lateral budding.” When a bud is elongating, a peak of Fgf10 expression is formed in the mesenchyme near the tip; whereas when terminal bifurcation and lateral budding occur, two separate peaks are formed instead. To explain the spatial pattern of Fgf10 expression, we developed a mathematical model for the regulation of Fgf10 expression with geometrical conditions including shapes of the lung buds and the lung border. Different localization patterns of Fgf10 expression can be explained by the geometrical conditions. Fgf10 expression has a single peak when a length between the tip of lung bud and the lung border is large. When the length is small, Fgf10 expression has two peaks, whose location depends on the curvature of lung border. Developmental Dynamics 238:2813–2822, 2009. © 2009 Wiley‐Liss, Inc.
Homozygous disruption of the tip60 gene causes early embryonic lethality
Authors: Hu Yaofei , Fisher Joseph B. , Koprowski Stacy , McAllister Donna , Kim Min‐Su , Lough John
Published: October 2009

Tat‐interactive protein 60 (Tip60) is a member of the MYST family, proteins of which are related by an atypical histone acetyltransferase (HAT) domain. Although Tip60 has been implicated in cellular activities including DNA repair, apoptosis, and transcriptional regulation, its function during embryonic development is unknown. We ablated the Tip60 gene (Htatip) from the mouse by replacing exons 1–9 with a neomycin resistance cassette. Development and reproduction of wild‐type and heterozygous animals were normal. However, homozygous ablation of the Tip60 gene caused embryolethality near the blastocyst stage of development, as evidenced by inability of cells in Tip60‐null blastocysts to hatch and survive in culture. Monitoring cell proliferation and death by detecting EdU‐substituted DNA and TUNEL labeling revealed suppression of cell proliferation concomitant with increased cell death as Tip60‐null cells attempted to hatch from blastocysts. These findings indicate that Tip60 is essential for cellular survival during the blastocyst‐gastrula transition of embryogenesis. Developmental Dynamics 238:2912–2921, 2009. © 2009 Wiley‐Liss, Inc.
Foxg1 is required for proper separation and formation of sensory cristae during inner ear development
Authors: Hwang Chan Ho , Simeone Antonio , Lai Eseng , Wu Doris K.
Published: October 2009

The vestibular portion of the inner ear, the three semicircular canals and their sensory cristae, is responsible for detecting angular head movements. It was proposed that sensory cristae induce formation of their non‐sensory components, the semicircular canals. Here, we analyzed the inner ears of Foxg1−/− mouse mutants, which display vestibular defects that are in conflict with the above model. In Foxg1−/− ears, the lateral canal is present without the lateral ampulla, which houses the lateral crista. Our gene expression analyses indicate that at the time when canal specification is thought to occur, the prospective lateral crista is present, which could have induced lateral canal formation prior to its demise. Our genetic fate‐mapping analyses indicate an improper separation between anterior and lateral cristae in Foxg1−/− mutants. Our data further suggest that a function of Foxg1 in the inner ear is to restrict sensory fate. Developmental Dynamics 238:2725–2734, 2009. © 2009 Wiley‐Liss, Inc.
Osteoblast maturation occurs in overlapping proximal‐distal compartments during fin regeneration in zebrafish
Authors: Brown Andrew M. , Fisher Shannon , Kathryn Iovine M.
Published: October 2009

During fin regeneration, osteoblasts must continually differentiate for outgrowth of the bony fin rays. Bone maturity increases in a distal‐proximal manner, and osteoblast maturation can be detected similarly when following gene expression. We find that early markers for osteoblast differentiation are expressed in a discrete domain at the distal end of the fin, just proximal to the adjacent germinal compartment of dividing cells. Matrix genes, required at later stages developmentally, are expressed in a population of cells proximally to the early genes. A marker for mature osteoblasts is expressed in cells further proximal. These domains of gene expression are partially overlapping, perhaps revealing additional levels of osteoblast maturity. We suggest a model for growth where new cells are continually added to the distal‐most osteoblast compartment, while osteoblasts in more proximal locations differentiate, thus translating developmental time to location on the proximal‐distal axis. Developmental Dynamics 238:2922–2928, 2009. © 2009 Wiley‐Liss, Inc.
Developmental expression of Smoc1 and Smoc2 suggests potential roles in fetal gonad and reproductive tract differentiation
Authors: Pazin Dorothy E. , Albrecht Kenneth H.
Published: October 2009

SMOC1 and SMOC2 are matricellular proteins thought to influence growth factor signaling, migration, proliferation, and angiogenesis. We examined the expression and regulation of Smoc1 and Smoc2 in fetal gonad/mesonephros complexes to discover possible roles for these genes in gonad and mesonephros development. Smoc1 was upregulated at ∼E10.75 in a center‐to‐poles wave in pre‐Sertoli and pre‐granulosa cells and its expression was greatly reduced in Wt1, Sf1, and Fog2 mutants. After E13.5, Smoc1 was downregulated in an anterior‐to‐posterior wave in granulosa cells but persisted in Sertoli cells, suggesting a sexually dimorphic requirement in supporting cell lineage differentiation. Smoc2 was expressed in Leydig cells, mesonephroi, and Wnt4 mutant ovaries, but not wildtype ovaries. Using organ culture, we determined that Smoc2 expression was dependent on Hedgehog signaling in testes, mesonephroi, and kidneys. Overall, these results demonstrate that SMOC1 and SMOC2 may mediate intercellular signaling and cell type–specific differentiation during gonad and reproductive tract development. Developmental Dynamics 238:2877–2890, 2009. © 2009 Wiley‐Liss, Inc.
Pain severity in eating disorders predicts longer inpatient hospitalization
Authors: Coughlin Janelle W. , Edwards Robert R. , Redgrave Graham W. , Guarda Angela S.
Published: October 2009

Objective

This study examined pain intensity (PI) in eating disorders.

Method

Comparisons between inpatients (N = 208) reporting moderate to severe pain (HiP) and no pain or mild pain (LoP) at admission were made, and the relationship between PI and treatment response was examined.

Results

Patients with HiP were older, had a greater likelihood of having a bingeing and/or purging diagnosis, and reported greater body dissatisfaction, drive for thinness, depressive symptomatology, and neuroticism in comparison to those with LoP. They were also more likely to report widespread pain, to catastrophize about pain and to use praying and hoping to cope with pain. PI was associated with longer length of inpatient hospitalization, even after controlling for degree of underweight, depressive symptomatology, and neurotic personality features.

Discussion

This is the first observation of a relationship between pain and health care utilization in eating disorders. The results imply that pain management is an important component of treatment. © 2009 by Wiley Periodicals, Inc. Int J Eat Disord 2010; 43:737–742
Effects of Microrna-29 on Apoptosis, Tumorigenicity, and Prognosis of Hepatocellular Carcinoma
Authors: Xiong Yujuan , Fang Jian-Hong , Yun Jing-Ping , Yang Jine , Zhang Ying , Jia Wei-Hua , Zhuang Shi-Mei
Published: October 2009

Based on microarray data, we have previously shown a significant down-regulation of miR-29 in hepatocellular carcinoma (HCC) tissues. To date, the role of miR-29 deregulation in hepatocarcinogenesis and the signaling pathways by which miR-29 exerts its function and modulates the malignant phenotypes of HCC cells remain largely unknown. In this study, we confirmed that reduced expression of miR-29 was a frequent event in HCC tissues using both Northern blot and real-time quantitative reverse-transcription polymerase chain reaction. More interestingly, we found that miR-29 down-regulation was significantly associated with worse disease-free survival of HCC patients. Both gain- and loss-of-function studies revealed that miR-29 could sensitize HCC cells to apoptosis that was triggered by either serum starvation and hypoxia or chemotherapeutic drugs, which mimicked the tumor growth environment

in vivo

and the clinical treatment. Moreover, introduction of miR-29 dramatically repressed the ability of HCC cells to form tumor in nude mice. Subsequent investigation characterized two antiapoptotic molecules, Bcl-2 and Mcl-1, as direct targets of miR-29. Furthermore, silencing of Bcl-2 and Mcl-1 phenocopied the proapoptotic effect of miR-29, whereas overexpression of these proteins attenuated the effect of miR-29. In addition, enhanced expression of miR-29 resulted in the loss of mitochondrial potential and the release of cytochrome c to cytoplasm, suggesting that miR-29 may promote apoptosis through a mitochondrial pathway that involves Mcl-1 and Bcl-2.

Conclusion:

Our data highlight an important role of miR-29 in the regulation of apoptosis and in the molecular etiology of HCC, and implicate the potential application of miR-29 in prognosis prediction and in cancer therapy. (Hepatology 2010.)
Concise Synthesis of [1,1′‐Biisoquinoline]‐4,4′‐diol via a Protecting Group Strategy and Its Application for Potential Liquid‐Crystalline Compounds
Authors: Kapatsina Elisabeth , Mateescu Markus , Baro Angelika , Frey Wolfgang , Laschat Sabine
Published: October 2009

The [1,1′‐biisoquinoline]‐4,4′‐diol (4a), which was obtained as hydrochloride 4a⋅2 HCl in two steps starting from the methoxymethyl (MOM)‐protected 1‐chloroisoquinoline 8 (Scheme 3), opens access to further O‐functionalized biisoquinoline derivatives. Compound 4a⋅2 HCl was esterified with 4‐(hexadecyloxy)benzoyl chloride (5b) to give the corresponding diester 3b (Scheme 4), which could not be obtained by Ni‐mediated homocoupling of 6b (Scheme 2). The ether derivative 2b was accessible in good yield by reaction of 4a⋅2 HCl with the respective alkyl bromide 9 under the conditions of Williamson etherification (Scheme 4). Slightly modified conditions were applied to the esterification of 4a⋅2 HCl with galloyl chlorides 10a–h as well as etherification of 4a⋅2 HCl with 6‐bromohexyl tris(alkyloxy)benzoates 11b,d–h and [(6‐bromohexyl)oxy]‐substituted pentakis(alkyloxy)triphenylenes 14a–c (Scheme 5). Despite the bulky substituents, the respective target 1,1′‐biisoquinolines 12, 13, and 15 were isolated in 14–86% yield (Table).