bluuebunny/crossref_metadata_2025 huggingface dataset:
Fat Mass Exerts a Greater Effect on Cortical Bone Mass in Girls than Boys
Authors: Sayers Adrian , Tobias Jonathan H.
Published: December 2009

Context: It is unclear whether fat mass (FM) and lean mass (LM) differ in the way they influence cortical bone development in boys and girls.

Objective: The aim of the study was to investigate the contributions of total body FM and LM to parameters related to cortical bone mass and geometry.

Design/Setting: We conducted a longitudinal birth cohort study, the Avon Longitudinal Study of Parents and Children.

Participants: A total of 4005 boys and girls (mean age, 15.5 yr) participated in the study.

Outcome Measures: We measured cortical bone mass, cortical bone mineral content (BMCC), cortical bone mineral density, periosteal circumference (PC), and endosteal circumference by tibial peripheral quantitative computed tomography.

Results: LM had a similar positive association with BMCC in boys and girls [regression coefficients with 95% confidence interval (CI); P for gender interactions: boys/girls, 0.952 (0.908, 0.997); P = 0.85]. However, the mechanisms by which LM influenced bone mass differed according to gender because LM was positively associated with PC more strongly in girls [boys, 0.579 (0.522, 0.635); girls, 0.799 (0.722, 0.875); P < 0.0001], but was only associated with cortical bone mineral density in boys [boys, 0.443 (0.382, 0.505); girls, 0.014 (−0.070, 0.097); P < 0.0001]. There was a stronger positive association between FM and BMCC in girls [boys, 0.227 (0.185, 0.269); girls, 0.355 (0.319, 0.392); P < 0.0001]. This reflected both a greater positive association of FM with PC in girls [boys, 0.213 (0.174, 0.253); girls, 0.312 (0.278, 0.347); P = 0.0002], and a stronger negative association with endosteal circumferencePC [boys, −0.059 (−0.096, 0.021); girls, −0.181 (−0.215, −0.146); P < 0.0001].

Conclusions: Whereas LM stimulates the accrual of cortical bone mass to a similar extent in boys and girls, FM is a stronger stimulus for accrual of cortical bone mass in girls, reflecting a greater tendency in females for FM to stimulate periosteal growth and suppress endosteal expansion.
The role of unorthodox and traditional birth care in maternal mortality
Authors: Umeora O U J , Egwuatu V E
Published: December 2009

Many pregnant women see unorthodox medical providers in labour before presentation to the modern medical facilities after obstetric complications have arisen. This study evaluates the contribution of unorthodox medical facilities to the delays subsisting maternal mortality in a rural, poor and illiterate community. Data was collected prospectively on all referrals from outside the St. Vincent's hospital, over a three-year period. Seven hundred and fifty women were referred to the hospital and there were a total of thirty maternal deaths out of the 1268 live births, giving a maternal mortality ratio of 2366/100,000. Most of the referrals were patient-driven and verbal and came from traditional birth attendants (TBAs). The majority of the patients (86.7%) came in poor clinical conditions and some were moribund. The TBAs contributed most to maternal deaths. Prolongation of labour for more than 24 hours correlated positively with maternal mortality. Ruptured uterus complicating obstructed labour (34.8%) and haemorrhage (30.4%) were the leading causes of death in this series. The mortal delay suffered by pregnant women in accessing unorthodox medical attention deserves further attention in issues of maternal mortality in the underserved rural communities of Nigeria.
Peripartum hysterectomy: a ten-year experience at a tertiary care hospital in a developing country
Authors: Saeed Ferha , Khalid Roha , Khan Abdullah , Masheer Shazia , Rizvi Javed H
Published: December 2009

Acute bleeding after delivery can be a life-threatening complication. Emergency hysterectomy is usually undertaken as a last resort. This study was conducted in order to estimate the incidence, indications, risk factors and complications associated with peripartum hysterectomy performed at a tertiary care hospital. We retrospectively analysed 39 of 45 cases of emergency peripartum hysterectomy performed at the Aga Khan University Hospital from 1997–2006. Peripartum hysterectomy was defined as one performed for a haemorrhage after delivery which is unresponsive to other treatments. The most frequent indications for peripartum hysterectomy were morbidly adherent placenta (46%) and uterine atony (23%). The duration of surgery was shorter ( P = 0.045) but the complications were higher ( P = 0.029) in total compared with subtotal hysterectomies. Our results suggest that caesarean deliveries are associated with an increased risk for peripartum hysterectomy, which is of concern given the increasing rate of caesarean deliveries. Subtotal hysterectomy is a reasonable alternative in emergency obstetric hysterectomy.
Barriers to follow-up of abnormal Papanicolaou smears among women in Leon, Nicaragua
Authors: Vastbinder M B , Castillo C , Bekkers R L M
Published: December 2009

Cervical cancer screening programmes only succeed when the coverage, screening, treatment and follow-up of any abnormal results are of high quality. This study investigates the screening coverage and the quality of the follow-up of cervical cancer screening of women in León, Nicaragua, as well as the factors affecting coverage and barriers to follow-up. Two hundred and thirty-four sexually active women attending a public health centre (54), a public health post (63), or the gynaecology department of the public HEODRA hospital (117), were invited to answer an orally administered questionnaire. The screening coverage of cervical cancer was calculated and the follow-up after finding an abnormal screening result was assessed. The coverage was 60.6% (95% confidence interval 54.4–66.8%). One hundred and sixty-eight women (87%) were informed about the results. Eighteen (10, 7%) of the women who were informed about the results, were advised to have follow-up and 12 (66, 7%) of them did. Barriers to follow-up were financial constraints, pregnancy, postponement and absence of instruments/electricity. This study shows that the screening coverage and cytology services are adequate, but that there is insufficient follow-up and/or treatment after an abnormal screening result. In order to achieve a lower incidence and mortality of cervical cancer, follow-up and treatment after an abnormal screening result need to be improved. A visual inspection with acetic acid may be an attractive alternative.
Adiponectin and cardiac geometry and function in elderly: results from two community-based cohort studies
Authors: Gustafsson Stefan , Lind Lars , Zethelius Björn , Venge Per , Flyvbjerg Allan , Söderberg Stefan , Ingelsson Erik
Published: December 2009

Objective

Several smaller studies have indicated that adiponectin might be associated with left ventricular (LV) mass and function, but community-based studies with adequate sample size and adjustment for potential confounders are lacking. Our objective was to investigate such associations in two large community-based studies of elderly.

Design

Cross-sectional.

Methods

We evaluated cross-sectional relations between serum adiponectin and echocardiographic measures of cardiac geometry and function (LV mass index, LV relative wall thickness, LV end-diastolic diameter, left atrial diameter, ejection fraction, LV isovolumic relaxation time, and E/A ratio) in 954 70-year-old participants (50% women) of the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS), and in 427 71-year-old men from the Uppsala Longitudinal Study of Adult Men (ULSAM).

Results

In models adjusted for age, sex, body mass index, systolic blood pressure, antihypertensive treatment, antidiabetic treatment, lipid-lowering medication, fasting blood glucose, total cholesterol, high-density lipoprotein cholesterol, creatinine, and smoking, adiponectin was inversely associated with ejection fraction in men (β, −1.62; 95% confidence interval (CI), −2.50, −0.75 in PIVUS; β, −1.35; 95% CI, −2.41, −0.29 in ULSAM), but not in women. After additional adjustment for N-terminal pro-brain natriuretic peptide (NT-proBNP), the association between adiponectin and ejection fraction was attenuated (β, −0.98; 95% CI, −1.86, −0.10 in PIVUS; β, −0.75; 95% CI, −1.84, 0.35 in ULSAM).

Conclusions

Serum adiponectin concentrations were associated with ejection fraction in men, and these associations were partially attenuated by NT-proBNP. Our results imply that adiponectin may be associated with systolic function through pathways that involve natriuretic peptides.
Intraperitoneal VEGF Inhibition Using Bevacizumab: A Potential Approach for the Symptomatic Treatment of Malignant Ascites?
Authors: Kobold Sebastian , Hegewisch-Becker Susanna , Oechsle Karin , Jordan Karin , Bokemeyer Carsten , Atanackovic Djordje
Published: December 2009

Despite overall improvements in oncological care in the palliative setting, symptomatic malignant ascites remains a severe clinical problem. This form of effusion is known to be widely resistant to established modes of systemic therapy. Accordingly, frequent paracentesis often represents the only effective way for symptom relief in patients with advanced cancer. This invasive mode of therapy, however, is often very burdensome for the patient who is already severely distressed by the underlying malignancy. Recently, the trifunctional monoclonal antibody catumaxomab given i.p. has shown symptom relief in patients with ovarian cancer and malignant ascites. On another front, the release of vascular endothelial growth factor (VEGF) by tumor cells has been identified as a main factor promoting the i.p. secretion of fluid. Accordingly, recent evidence suggests that targeting VEGF may have the potential to suspend the ascites production resulting from peritoneal metastasis. Here, we review preclinical and clinical data supporting this hypothesis. We show current evidence suggesting that the i.p. application of the anti-VEGF antibody bevacizumab, which is already in use as an i.v. therapeutic drug for a variety of tumors, might represent an effective way to prevent local fluid accumulation. Because such an effect would result in significant relief for patients, future clinical studies should stringently assess the effectiveness of this targeted therapy for the treatment of malignant i.p. effusions.
Systemic therapy for neuroendocrine tumours of gastroenteropancreatic origin
Authors: Basu Bristi , Sirohi Bhawna , Corrie Pippa
Published: December 2009

Systemic therapy is one of a number of treatment options routinely used in the management of advanced, unresectable neuroendocrine tumours (NETs). In contrast to many of the other NET treatment modalities, there is at least some evidence base to justify its use. Even so, well-designed clinical trials are limited, since conducting clinical research in this complex group of rare cancers is challenging. The remit of this review article is to summarise the oncology literature and explain the role of systemic therapy in treating NETs of gastroenteropancreatic origin, identifying benefits and limitations. The molecular biology of NETs is now being unravelled, which affords new opportunities for development of mechanism-driven therapies. The rationale for some of the newer systemic targeted therapies that are showing promise in the clinic is discussed.
Effect-like algebras induced by means of basic algebras
Authors: Chajda Ivan
Published: December 2009

Having an MV-algebra, we can restrict its binary operation addition only to the pairs of orthogonal elements. The resulting structure is known as an effect algebra, precisely distributive lattice effect algebra. Basic algebras were introduced as a generalization of MV-algebras. Hence, there is a natural question what an effect-like algebra can be reached by the above mentioned construction if an MV-algebra is replaced by a basic algebra. This is answered in the paper and properties of these effect-like algebras are studied.
Cutting Edge: Vascular Endothelial Growth Factor-Mediated Signaling in Human CD45RO+ CD4+ T Cells Promotes Akt and ERK Activation and Costimulates IFN-γ Production
Authors: Basu Aninda , Hoerning Andre , Datta Dipak , Edelbauer Monika , Stack Maria P. , Calzadilla Katiana , Pal Soumitro , Briscoe David M.
Published: December 2009

In this study, we find that CD45RO+ memory populations of CD4+ T lymphocytes express the vascular endothelial growth factor (VEGF) receptors KDR and Flt-1 at both the mRNA and protein levels. Furthermore, by Western blot analysis, we find that VEGF increases the phosphorylation and activation of ERK and Akt within CD4+CD45RO+ T cells. These VEGF-mediated signaling responses were inhibited by a KDR-specific small interfering RNA in a VEGF receptor-expressing Jurkat T cell line and by SU5416, a pharmacological KDR inhibitor, in CD4+CD45RO + T cells. We also find that VEGF augments mitogen-induced production of IFN-γ in a dose-dependent manner (p < 0.001) and significantly (p < 0.05) increases directed chemotaxis of this T cell subset. Collectively, our results for the first time define a novel function for VEGF and KDR in CD45RO+ memory T cell responses that are likely of great pathophysiological importance in immunity.
Nucleotide Oligomerization Binding Domain-Like Receptor Signaling Enhances Dendritic Cell-Mediated Cross-Priming In Vivo
Authors: Asano Jumpei , Tada Hiroyuki , Onai Nobuyuki , Sato Taku , Horie Yasuo , Fujimoto Yukari , Fukase Koichi , Suzuki Akira , Mak Tak W. , Ohteki Toshiaki
Published: December 2009

Nucleotide oligomerization binding domain (Nod)-like receptors are critical cytosolic sensors for the recognition of bacterial peptidoglycan. However, their role in the induction of dendritic cell (DC)-mediated cross-priming remains unclear. In this study, we demonstrate that injecting ligands for Nod1 and Nod2 along with Ag into wild-type mice significantly enhanced the cross-priming of Ag-specific CD8+ T cells by CD8α+ DCs, as assessed from the expansion of IFN-γ+ CD8+ T cells, CTL activity against Ag-pulsed targets, and the rejection of transplanted tumors expressing the cognate Ag. The enhancement of CD8α+ DC-mediated cross-priming was likely due to the upregulation of Ag cross-presentation and of costimulatory molecules. Our findings collectively indicate that Nod1/2 signaling is critical for the optimal induction of DC cross-priming in vivo, which may offer an alternative therapeutic pathway in cancer and hosts refractory to TLR signals or paralyzed by viral evasion strategy.
Factor H and Factor H-Related Protein 1 Bind to Human Neutrophils via Complement Receptor 3, Mediate Attachment to Candida albicans, and Enhance Neutrophil Antimicrobial Activity
Authors: Losse Josephine , Zipfel Peter F. , Józsi Mihály
Published: December 2009

The host complement system plays an important role in protection against infections. Several human-pathogenic microbes were shown to acquire host complement regulators, such as factor H (CFH), that downregulate complement activation at the microbial surface and protect the pathogens from the opsonic and lytic effects of complement. Because CFH can also bind to host cells, we addressed the role of CFH and CFH-related proteins as adhesion ligands in host-pathogen interactions. We show that the CFH family proteins CFH, CFH-like protein 1 (CFHL1), CFH-related protein (CFHR) 1, and CFHR4 long isoform bind to human neutrophil granulocytes and to the opportunistic human-pathogenic yeast Candida albicans. Two major binding sites, one within the N-terminus and one in the C-terminus of CFH, were found to mediate binding to neutrophils. Complement receptor 3 (CD11b/CD18; αMβ2 integrin) was identified as the major cellular receptor on neutrophils for CFH, CFHL1, and CFHR1, but not for CFHR4 long isoform. CFH and CFHR1 supported cell migration. Furthermore, CFH, CFHL1, and CFHR1 increased attachment of neutrophils to C. albicans. Adhesion of neutrophils to plasma-opsonized yeasts was reduced when CFH binding was inhibited by specific Abs or when using CFH-depleted plasma. Yeast-bound CFH and CFHR1 enhanced the generation of reactive oxygen species and the release of the antimicrobial protein lactoferrin by human neutrophils, and resulted in a more efficient killing of the pathogen. Thus, CFH and CFHR1, when bound on the surface of C. albicans, enhance antimicrobial activity of human neutrophils.
CD56highCD16−CD62L− NK Cells Accumulate in Allergic Contact Dermatitis and Contribute to the Expression of Allergic Responses
Authors: Carbone Teresa , Nasorri Francesca , Pennino Davide , Eyerich Kilian , Foerster Stefanie , Cifaldi Loredana , Traidl-Hoffman Claudia , Behrendt Heidrun , Cavani Andrea
Published: December 2009

Allergic contact dermatitis is a common disease caused by an exaggerated T cell-mediated immune response to skin-applied haptens. We show in this study that NK cells affect skin immune responses to haptens by releasing type 1 cytokines and inducing keratinocytes apoptosis. Immunohistochemical stainings demonstrated that NK lymphocytes constitute ∼10% of the inflammatory infiltrate mostly distributed in the superficial dermis and in the epidermis at the site of intense spongiotic changes. More than 90% of NK cells isolated from allergic contact dermatitis skin showed a CD3-CD56highCD16− phenotype by FACS analysis. In addition, they uniformly expressed NKG2A, intermediate to high levels of perforin, and the activating receptors, NKG2D, NKp44, and NKp46, but lacked NKp30 and killer Ig-related receptors. Skin NK lymphocytes displayed a CXCR3+CCR6+CCR5+ chemokine receptor asset for homing into inflamed skin, but not CD62L and CCR7 for lymph node homing. When NK cells from nickel-allergic donors were exposed in vitro to the metal, they failed to proliferate, to upregulate CD69, and to release IFN-γ, thus indicating that NK lymphocytes do not exhibit memory-like properties to haptens. However, IL-2 released by hapten-driven T lymphocytes rapidly induced the release of IFN-γ by NK cells and promoted the NK-mediated apoptosis of autologous keratinocytes in a hapten-independent manner. Our findings underline the importance of the interaction between innate and adaptive immune mechanisms for amplification of skin allergic responses to haptens and full expression of allergic contact dermatitis
IFN-γ–Dependent Activation of Macrophages during Experimental Infections by Mycobacterium ulcerans Is Impaired by the Toxin Mycolactone
Authors: Torrado Egídio , Fraga Alexandra G. , Logarinho Elsa , Martins Teresa G. , Carmona Jenny A. , Gama José B. , Carvalho Maria A. , Proença Fernanda , Castro Antonio G. , Pedrosa Jorge
Published: December 2009

Buruli ulcer, caused by Mycobacterium ulcerans infections, is a necrotizing skin disease whose pathogenesis is associated with the exotoxin mycolactone. Despite the relevance of this emergent disease, little is known on the immune response against the pathogen. Following the recent demonstration of an intramacrophage growth phase for M. ulcerans, we investigated the biological relevance of IFN-γ and the antimycobacterial mechanisms activated by this cytokine in M. ulcerans-infected macrophages. Three M. ulcerans strains were tested: 5114 (mutant mycolactone-negative, avirulent strain); 94–1327 (intermediate virulence); and 98–912 (high virulence). We show in this study that IFN-γ is expressed in mouse-infected tissues and that IFN-γ–deficient mice display increased susceptibility to infection with strains 5114 and, to a lesser extent, 94–1327, but not with the highly virulent strain. Accordingly, IFN-γ–activated cultured macrophages controlled the proliferation of the avirulent and the intermediate virulent strains. Addition of mycolactone purified from strain 98–912 to cultures of IFN-γ–activated macrophages infected with the mycolactone-negative strain led to a dose-dependent inhibition of the IFN-γ–induced protective mechanisms, involving phagosome maturation/acidification and increased NO production, therefore resulting in increased bacterial burdens. Our findings suggest that the protection mediated by IFN-γ in M. ulcerans-infected macrophages is impaired by the local buildup of mycolactone.
Vitamin D Decreases Respiratory Syncytial Virus Induction of NF-κB–Linked Chemokines and Cytokines in Airway Epithelium While Maintaining the Antiviral State
Authors: Hansdottir Sif , Monick Martha M. , Lovan Nina , Powers Linda , Gerke Alicia , Hunninghake Gary W.
Published: December 2009

Epidemiological studies suggest that low vitamin D levels may increase the risk or severity of respiratory viral infections. In this study, we examined the effect of vitamin D on respiratory syncytial virus (RSV)-infected human airway epithelial cells. Airway epithelium converts 25-hydroxyvitamin D3 (storage form) to 1,25-dihydroxyvitamin D3 (active form). Active vitamin D, generated locally in tissues, is important for the nonskeletal actions of vitamin D, including its effects on immune responses. We found that vitamin D induces IκBα, an NF-κB inhibitor, in airway epithelium and decreases RSV induction of NF-κB–driven genes such as IFN-β and CXCL10. We also found that exposing airway epithelial cells to vitamin D reduced induction of IFN-stimulated proteins with important antiviral activity (e.g., myxovirus resistance A and IFN-stimulated protein of 15 kDa). In contrast to RSV-induced gene expression, vitamin D had no effect on IFN signaling, and isolated IFN induced gene expression. Inhibiting NF-κB with an adenovirus vector that expressed a nondegradable form of IκBα mimicked the effects of vitamin D. When the vitamin D receptor was silenced with small interfering RNA, the vitamin D effects were abolished. Most importantly we found that, despite inducing IκBα and dampening chemokines and IFN-β, there was no increase in viral mRNA or protein or in viral replication. We conclude that vitamin D decreases the inflammatory response to viral infections in airway epithelium without jeopardizing viral clearance. This suggests that adequate vitamin D levels would contribute to reduced inflammation and less severe disease in RSV-infected individuals.
Glycogen Synthase Kinase 3β Activation Is a Prerequisite Signal for Cytokine Production and Chemotaxis in Human Mast Cells
Authors: Rådinger Madeleine , Kuehn Hye Sun , Kim Mi-Sun , Metcalfe Dean D. , Gilfillan Alasdair M.
Published: December 2009

In addition to regulating mast cell homeostasis, the activation of KIT following ligation by stem cell factor promotes a diversity of mast cell responses, including cytokine production and chemotaxis. Although we have previously defined a role for the mammalian target of rapamycin complex 1 in these responses, it is clear that other signals are also required for maximal KIT-dependent cytokine production and chemotaxis. In this study, we provide evidence to support a role for glycogen synthase kinase 3β (GSK3β) in such regulation in human mast cells (HuMCs). GSK3β was observed to be constitutively activated in HuMCs. This activity was inhibited by knockdown of GSK3β protein following transduction of these cells with GSK3β-targeted shRNA. This resulted in a marked attenuation in the ability of KIT to promote chemotaxis and, in synergy with FcεRI-mediated signaling, cytokine production. GSK3β regulated KIT-dependent mast cell responses independently of mammalian target of rapamycin. However, evidence from the knockdown studies suggested that GSK3β was required for activation of the MAPKs, p38, and JNK and downstream phosphorylation of the transcription factors, Jun and activating transcription factor 2, in addition to activation of the transcription factor NF-κB. These studies provide evidence for a novel prerequisite priming mechanism for KIT-dependent responses regulated by GSK3β in HuMCs.
DNAM-1/CD155 Interactions Promote Cytokine and NK Cell-Mediated Suppression of Poorly Immunogenic Melanoma Metastases
Authors: Chan Christopher J. , Andrews Daniel M. , McLaughlin Nicole M. , Yagita Hideo , Gilfillan Susan , Colonna Marco , Smyth Mark J.
Published: December 2009

A role for NK cells in therapeutic intervention for hematologic malignancies, such as acute myeloid leukemia and multiple myeloma, and nonhematologic malignancies, such as melanoma, is becoming more apparent. DNAM-1 is an NK cell receptor whose importance in facilitating activation signals received by NK cells in natural and cytokine-driven responses to tumor metastases in vivo is poorly explored. In this study, we used matched tumor lines expressing a variety of relevant ligands, neutralizing monoclonal Abs, and DNAM-1 gene-targeted mice to determine the relative importance of DNAM-1–ligand interactions in controlling tumor metastases. Our results demonstrate that NK cells require DNAM-1 for natural or cytokine (IL-2, IL-12, or IL-21) suppression of tumor metastases or their variants expressing CD70 or CD80. In contrast, DNAM-1 was dispensable when tumor cells were targets of Ab-dependent cellular cytotoxicity or presented ligands for NKG2D. CD155 appeared to be a key ligand recognized by DNAM-1 in NK cell-mediated suppression of metastases, and DNAM-1-mediated suppression coincided with perforin activity. Overall, these data implied a general role for DNAM-1-CD155 interactions in NK cell-mediated killing of tumors, even in the presence of tumor CD70 or CD80 expression, and further defined the optimal efficacy requirements of cytokines that directly activate NK cells.
Morphometric analysis and classification of the facial phenotype associated with fetal alcohol syndrome in 5‐ and 12‐year‐old children
Authors: Mutsvangwa Tinashe E.M. , Meintjes Ernesta M. , Viljoen Dennis L. , Douglas Tania S.
Published: December 2009

Landmark‐based morphometric analysis holds promise for quantitative assessment of craniofacial dysmorphology. We describe an application of facial shape analysis to characterize the facial anomalies associated with fetal alcohol syndrome (FAS) in a mixed ancestry population. Generalized Procrustes analysis, regression and discriminant function analysis were applied to stereo‐photogrammetrically derived 3D coordinates of landmarks taken from 34 subjects (n = 17 FAS and n = 17 normal controls). Four shape analyses were carried out, namely a comparison of the FAS and control facial shapes at age 5, and one at age 12; a comparison of the FAS facial shapes at ages 5 and 12; and a comparison of control facial shapes at ages 5 and 12. The first two analyses showed that the FAS face is characterized by small palpebral fissures, a thin upper lip, and midfacial hypoplasia. Classification of subjects as having FAS using leave‐one‐out cross‐validation showed that the 5‐year‐old group could be classified with 95.46% accuracy and the 12‐year‐olds with 80.13% accuracy. The third and fourth analyses revealed that the differences in facial shape between FAS individuals in different age groups were more pronounced than for control individuals, supporting the notion that FAS facial anomalies diminish with age. Geometric morphometric analysis of stereo‐photogrammetrically derived 3D facial landmarks allows visualization of the facial anomalies associated with FAS, as well as classification of facial shapes. © 2009 Wiley‐Liss, Inc.
Proceedings from the 2009 genetic syndromes of the Ras/MAPK pathway: From bedside to bench and back
Authors: Rauen Katherine A. , Schoyer Lisa , McCormick Frank , Lin Angela E. , Allanson Judith E. , Stevenson David A. , Gripp Karen W. , Neri Giovanni , Carey John C. , Legius Eric , Tartaglia Marco , Schubbert Suzanne , Roberts Amy E. , Gelb Bruce D. , Shannon Kevin , Gutmann David H. , McMahon Martin , Guerra Carmen , Fagin James A. , Yu Benjamin , Aoki Yoko , Neel Benjamin G. , Balmain Allan , Drake Richard R. , Nolan Garry P. , Zenker Martin , Bollag Gideon , Sebolt‐Leopold Judith , Gibbs Jackson B. , Silva Alcino J. , Patton E. Elizabeth , Viskochil David H. , Kieran Mark W. , Korf Bruce R. , Hagerman Randi J. , Packer Roger J. , Melese Teri
Published: December 2009

The RASopathies are a group of genetic syndromes caused by germline mutations in genes that encode components of the Ras/mitogen‐activated protein kinase (MAPK) pathway. Some of these syndromes are neurofibromatosis type 1, Noonan syndrome, Costello syndrome, cardio‐facio‐cutaneous syndrome, LEOPARD syndrome and Legius syndrome. Their common underlying pathogenetic mechanism brings about significant overlap in phenotypic features and includes craniofacial dysmorphology, cardiac, cutaneous, musculoskeletal, GI and ocular abnormalities, and a predisposition to cancer. The proceedings from the symposium “Genetic Syndromes of the Ras/MAPK Pathway: From Bedside to Bench and Back” chronicle the timely and typical research symposium which brought together clinicians, basic scientists, physician‐scientists, advocate leaders, trainees, students and individuals with Ras syndromes and their families. The goals, to discuss basic science and clinical issues, to set forth a solid framework for future research, to direct translational applications towards therapy and to set forth best practices for individuals with RASopathies were successfully meet with a commitment to begin to move towards clinical trials. © 2009 Wiley‐Liss, Inc.
Chemoselektivität und die eigentümlichen Reaktivitäten funktioneller Gruppen
Authors: Afagh Nicholas A. , Yudin Andrei K.
Published: December 2009

Mangelnde Chemoselektivität ist ein klassisches Problem der chemischen Synthese, und die Suche nach den richtigen Bedingungen, die unter oftmals vielfältigen Reaktionswegen den richtigen Mechanismus selektieren können, kennt jeder Praktiker als ein mühsames Unterfangen. Wir diskutieren in diesem Aufsatz verschiedene Aspekte der Chemoselektivität, die in den letzten rund zehn Jahren im Zusammenhang mit der Entwicklung diverser Synthesemethoden thematisiert worden sind. Unser Hauptaugenmerk gilt den Reaktionsmechanismen der zur Diskussion stehenden Prozesse, mit dem Versuch, diese zu kategorisieren und die Schlüsselkonzepte zu beleuchten, die aus diesen Studien hervorgegangen sind. Unsere Übersicht wird zeigen, dass erhebliche Fortschritte erzielt wurden, gleichzeitig aber noch große Herausforderungen vor uns liegen.
Relative clinical utility of three child symptom inventory‐4 scoring algorithms for differentiating children with autism spectrum disorder vs. attention‐deficit hyperactivity disorder
Authors: DeVincent Carla J. , Gadow Kenneth D.
Published: December 2009

Objective: The present study compared three separate Child Symptom Inventory‐4 (CSI‐4) scoring algorithms for differentiating children with autism spectrum disorder (ASD) from youngsters with attention‐deficit/hyperactivity disorder (ADHD). Method: Parents/teachers completed the CSI‐4, a DSM‐IV‐referenced rating scale, for 6 to 12‐year‐old clinical referrals with ASD (N=186) and ADHD (N=251). Algorithms were based on either all CSI‐4 items (forward logistic regressions) or the 12 DSM‐IV symptoms of pervasive developmental disorder (PDD) included in the CSI‐4. Results: ROC analyses indicated generally good to excellent values for area under the curve, sensitivity, specificity, and positive predictive power. Algorithms for parent ratings were superior to teacher ratings. The algorithm based solely on PDD symptoms evidenced the greatest generalizability. Conclusion: Although algorithms generated from regression analyses produced greater clinical utility for specific samples, the PDD‐based algorithm resulted in greater stability across samples.
Dimensionierung von maschinellen Tunnelvortrieben mit Tübbingausbau im Fels
Authors: Schmitt Jürgen , Stahlmann Joachim
Published: December 2009

In diesem Aufsatz werden auf theoretischer Grundlage abgeleitete Berechnungsansätze vorgestellt, durch die es möglich ist, das Risiko der Verklemmung des Schildmantels bei einer Tunnelbohrmaschine mit Schild (TBM‐S) beurteilen und die Größe des erforderlichen planmäßigen Überschnitts bemessen zu können. Ebenso werden analytische Berechnungsansätze für den Gebirgsdruck aufgeführt, die zu einer wirtschaftlicheren Dimensionierung der Tübbingsicherung für die zuvor genannte Vortriebsart beitragen können.

Dimensioning of shield tunnelling with segment lining in hard rock. In the available essay formulations based on theoretical elaborations are introduced, by which it is possible to estimate the risk of blocking of the shield skin of tunnel boring machine with shield (TBM‐S) and the size of the necessary regular overcut can calculated. Likewise analytic formulations for the ground pressure are specified, with which it is possible to design an economic segment lining for the kind of driving specified before.
Tragverhalten von horizontal belasteten Flügelpfählen
Authors: Dührkop Jan , Grabe Jürgen
Published: December 2009

Zur Verbesserung des horizontalen Last‐Verformungsverhaltens von Pfählen ist der Einsatz von Flügeln zur Aufweitung des Pfahlschafts im Pfahlkopfbereich eine sinnvolle Maßnahme. Der Bettungswiderstand wird im aufgeweiteten Bereich erhöht und die Verformung reduziert. In diesem Beitrag werden numerische Untersuchungen zur Verbesserung der Tragwirkung vorgestellt und ein Berechnungskonzept abgeleitet. Des Weiteren werden Feldversuche in Sand und Klei beschrieben, bei denen die Tragwirkung des Flügelpfahls messtechnisch dokumentiert wird. Es werden zudem Bemessungsdiagramme für Flügelpfähle in Sand vorgelegt.

On the response of laterally loaded piles with wings. The use of wings attached to the pile shaft near ground surface is a simple but effective way to improve the lateral pile response. The mobilised soil resistance in this section is significantly higher and the lateral deformation decreases. This paper presents numerical analysis of winged piles and a design method is outlined. Small‐scale field trials in sand and organic clay clearly point out the benefit of winged piles and proved the validity of the design method. Furthermore, design charts for a pre‐design of winged piles in sand are included.
Ein Modell zur Abschätzung der Tausetzung und der Kompressionseigenschaften aufgetauter Böden
Authors: Unold Florian
Published: December 2009

Es wird ein Berechnungsmodell zur quantitativen Bestimmung der Netto‐Tausetzung sowie der Druck‐Porenzahl‐Beziehung bei Weiterbelastung nach dem Auftauen feinkörniger Böden vorgestellt. Der Ansatz berücksichtigt die Inhomogenität der Veränderung des Bodengefüges infolge der Vereisung. Hierbei wird der Boden vereinfachend in zwei Bereiche unterteilt. Nach dem Modell wird ein Teil des Bodens mit einer rechnerischen Auflast, die der Summe der komprimierenden Vorgänge während der Bodenvereisung äquivalent ist, verdichtet. Für den übrigen Teil wird angenommen, dass er von der Vereisung unbeeinflusst bleibt. Die mit Hilfe des Modells ermittelten Berechnungsergebnisse stehen in sehr guter Übereinstimmung mit den Versuchsergebnissen. Der große Vorteil des Berechnungsansatzes liegt darin, dass eine zuverlässige Prognose der Kompressionseigenschaften des aufgetauten Bodens allein mit den Ergebnissen von Standard‐Laborversuchen möglich ist.

A model for the estimation of the thaw‐settlements and the compressibility properties of thawed soils. A mathematical model is presented which allows the quantitative calculation of the net thaw‐settlement as well as of the pressure‐void ratio relation at continued loading of fine grained soils after thawing. The approach takes into account the inhomogeneity of the change of the soil fabric caused by freezing. For this purpose, the soil is being divided into two parts, which is a simplification of the real situation. In the model, one part of the soil is being compacted with a load that is equivalent to the sum of all compressing processes during ground freezing. For the rest of the soil, it is assumed that it remains unaffected by freezing. The calculation results obtained by the model show good agreement with the results of laboratory tests. The great advantage of the introduced approach is that the compression properties of thawed soil can be reliably predicted just based on the results of standard laboratory tests.
Zum Erddruck auf Lawinenschutzgalerien
Authors: Kolymbas Dimitrios , Kirsch Ansgar
Published: December 2009

Eine Fehleinschätzung des Erddrucks auf überschüttete Galerien kann zu Schadensfällen führen. Im vorliegenden Beitrag wird ein analytischer Ansatz zur Prognose des Erddrucks auf Galerien vorgestellt. Grundlegende Annahme ist dabei, dass sich die Böschung aus kohäsionslosem Boden, in der sich die Galerie befindet, in einem Rankine'schen Spannungszustand befindet. Unter der weiteren Annahme einer reibungsfreien Kontaktfuge zwischen Galerie und Boden ergibt sich eine ausgeprägte Spitze in der Erddruckverteilung. Die Ausprägung der prognostizierten Spitze der Erddruckverteilung kann mit Finite‐Element‐Berechnungen nachvollzogen werden.

On the earth pressure on avalanche protection galleries. Structural damage of avalanche protection galleries is often attributed to misjudgement of the prevailing earth pressure. In this paper we present an analytical expression for the prediction of the earth pressure on avalanche protection galleries. The main assumption is that the soil surrounding the gallery is in a Rankine stress state. Under further assumption of a frictionless contact between soil and gallery, a distinct peak in the contact pressure on the gallery can be predicted. These findings are supported by a numerical parametric study with finite elements.
Einheit von Wissenschaft und Kunst im Brückenbau: Hellmut Homberg (1909–1990) – Sein Beitrag zur Theorie des Brückenbaus (Teil II)
Authors: Kurrer Karl‐Eugen , Pelke Eberhard , Stiglat Klaus
Published: December 2009

Aus dem baustatischen ŒuvreHombergs ragt sein Beitrag zur Theorie hochgradig statisch unbestimmter Trägerroste hervor, der im Folgenden im Zusammenhang mit der Entwicklung im Brückenbau und der Baustatik von den 1930‐er bis in die 1960‐er Jahre herausgearbeitet wird.

Harmony between science and art in bridge‐building: Hellmut Homberg (1909–1990) – his contribution to the theory of bridges (part II).The one theory of Hellmut Homberg that stands out from the rest of his contributions to the theory of structures is that concerning grillages with a high degree of static indeterminacy. This is described below in conjunction with the development of bridge‐building and theory of structures from the 1930s to the 1960s.
Geschichte und Evolution der Lactose(in)toleranz. Das Erbe der frühen Viehzüchter
Authors: Höffeler Fritz
Published: December 2009

Die Fähigkeit, auch im Erwachsenenalter noch Lactose verarbeiten zu können, basiert auf Punktmutationen in einem dem Lactase‐(LPH‐)Gen vorgelagerten Sequenzbereich, der Bindestellen für Regulatorproteine enthält. Die Ursache für die weltweit sehr uneinheitliche Verteilung der Lactase‐Persistenz liegt in der europäischen Menschheitsgeschichte: Im Verlauf des 8. vorchristlichen Jahrtausends entwickelte sich im Nahen Osten innerhalb einer größtenteils lactoseintoleranten Population eine Tradition der Milchviehzucht und des Milchverzehrs. Durch den starken Selektionsdruck auf die Lactosetoleranz verbreiteten sich die mutierten Allele sehr schnell. Während des 7. Jahrtausends v. Chr. begannen etliche dieser Populationen sukzessiv Europa zu besiedeln. Auch im nordöstlichen Afrika und auf der arabischen Halbinsel entstand eine Milchwirtschaft, die jedoch auf anderen Mutationen basiert.
Telomere: Ende gut, alles gut
Authors: Zacharias Helmut , Kronberg Inge
Published: December 2009

Die Verleihung des Nobelpreises in Physiologie oder Medizin an Elizabeth H. Blackburn, Jack W. Szostak und Carol W. Greider am 10. Dezember 2009 in Stockholm war nicht das Ende, sondern der Höhepunkt eines märchenhaften Verlaufes der Telomer‐ und Telomeraseforschung. Die Aufklärung von Bau und Synthese der Telomere hat in den vergangenen Jahrzehnten wesentliche Impulse für Krebs‐, Stammzell‐ und Seneszenzforschung geliefert.
Springspinne Bagheera kiplingi: Vegetarier auf acht Beinen
Authors: Wendler Silke
Published: December 2009

Die Forschergruppe um Christopher J. Meehan staunte nicht schlecht, als sie in Mexiko und Costa Rica eine Spinnenart entdeckten, die sich überwiegend vegetarisch ernährt. Die zu den Springspinnen gehörende Art Bagheera kiplingi “erbeutet” lieber Futterkörperchen von Akazienblättern, als Insekten nachzustellen.
Zur Einführung biowissenschaftlicher Bachelor‐ und Masterstudiengänge
Authors: Volke Beate , Gropengießer Harald
Published: December 2009

Welche Folgen hat die Umstellung der Studiengänge auf das Bachelor‐/Master‐System für das Biologiestudium? Antworten darauf gibt eine Umfrage der Universität Hannover: Im Sommersemester 2008 wurden die Studiendekane beziehungsweise die Studiengangskoordinatoren an 53 deutschen Hochschulen, an denen biowissenschaftliche Studiengänge angeboten werden, schriftlich befragt. Der Fragebogen enthielt Fragen mit Antwortvorgaben, mit halboffener und offener Beantwortung. Eine Rücklaufquote von nahezu 76 % verspricht einen verlässlichen Eindruck der Lage in den biowissenschaftlichen Studiengängen.
Nachrichten des Verbandes Biologie, Biowissenschaften & Biomedizin in Deutschland
Authors: Tautz Diethard
Published: December 2009

Aus den Fachgesellschaften

Nachgefragt: Deutsche Botanische Gesellschaft

Ausbildung und Karriere

VBIO verleiht BIOTECHNICA Studienpreis

Bilingualer Biologieunterricht im Aufwind

Taxonomen: Wo sind sie geblieben?
Corporate sustainability, ecological modernization and the policy process in the South African automotive industry
Authors: Kehbila Anderson Gwanyebit , Ertel Jürgen , Brent Alan Colin
Published: December 2009

In the past decade, the plea for corporate sustainability has gathered momentum and protecting the environment is one aspect for organizations to address if they are to conduct business in a sustainable manner. In this paper, we present the results of a questionnaire survey on the state of corporate sustainability within the South African automotive industry. The survey focused on the meaning and relevance of sustainability to South African automotive companies, and their use of different approaches to implement sustainability in corporate practice. On this score, the paper seeks to analyze and compare the levels of voluntary environmental initiatives between large and small and medium‐sized enterprises within the automotive milieu. Survey results reveal that a majority of automotive companies have sought to improve their environmental performance by integrating environmental considerations into their core activities. Although the majority of these companies have standardized EMSs, our analysis reveals considerable differences between companies' approaches to corporate sustainability. In particular, they varied in the extent to which procedures were formalized and documented behind the corporate rhetoric of a high commitment to sustainability. The paper concludes by prescribing a number of recommendations as to how to engage and promote more widely the South African automobile manufacturing companies in environmental change. Copyright © 2009 John Wiley & Sons, Ltd and ERP Environment.
Maintenance of pluripotency in mouse embryonic stem cells cultivated in stirred microcarrier cultures
Authors: Marinho Paulo A. N. , Fernandes Aline M. , Cruz Juliana C. , Rehen Stevens K. , Castilho Leda R.
Published: December 2009

The development of efficient and reproducible culture systems for embryonic stem (ES) cells is an essential pre‐requisite for regenerative medicine. Culture scale‐up ensuring maintenance of cell pluripotency is a central issue, because large amounts of pluripotent cells must be generated to warrant that differentiated cells deriving thereof are transplanted in great amounts and survive the procedure. This study aimed to develop a robust scalable cell expansion system, using a murine embryonic stem cell line that is feeder‐dependent and adapted to serum‐free medium, thus representing a more realistic model for human ES cells. We showed that high concentrations of murine ES cells can be obtained in stirred microcarrier‐based spinner cultures, with a 10‐fold concentration of cells per volume of medium and a 5‐fold greater cell concentration per surface area, as compared to static cultures. No differences in terms of pluripotency and differentiation capability were observed between cells grown in traditional static systems and cells that were replated onto the traditional system after being expanded on microcarriers in the stirred system. This was verified by morphological analyses, quantification of cells expressing important pluripotency markers (Oct‐4, SSEA‐1, and SOX2), karyotype profile, and the ability to form embryoid bodies with similar sizes, and maintaining their intrinsic ability to differentiate into all three germ layers. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2010
High‐throughput screening techniques for rapid PEG‐based precipitation of IgG4 mAb from clarified cell culture supernatant
Authors: Knevelman Carol , Davies Jim , Allen Lee , Titchener‐Hooker Nigel J.
Published: December 2009

Locating optimal protein precipitation conditions for complex biological feed materials is problematic. This article describes the application of a series of high‐throughput platforms for the rapid identification and selection of conditions for the precipitation of an IgG4 monoclonal antibody (mAb) from a complex feedstock using only microliter quantities of material. The approach uses 96‐microwell filter plates combined with high‐throughput analytical methods and a method for well volume determination for product quantification. The low material, time and resource requirements facilitated the use of a full factorial Design of Experiments (DoE) for the rapid investigation into how critical parameters impact the IgG4 precipitation. To aid the DoE, a set of preliminary range‐finding studies were conducted first. Data collected through this approach describing Polyethylene Glycol (PEG) precipitation of the IgG4 as a function of mAb concentration, precipitant concentration, and pH are presented. Response surface diagrams were used to explore interactions between parameters and to inform selection of the most favorable conditions for maximum yield and purification. PEG concentrations required for maximum yield and purity were dependant on the IgG4 concentration; however, concentrations of 14 to 20% w/v, pH 6.5, gave optimal levels of yield and purity. Application of the high‐throughput approach enabled 1,155 conditions to be examined with less than 1 g of material. The level of insights gained over such a short time frame is indicative of the power of microwell experimentation in allowing the rapid identification of appropriate processing conditions for key bioprocess operations. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2010