bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of SKAP-HOM in DCs is required for an optimal immune response in vivo
Authors: Reinhold Annegret , Reimann Sibylle , Reinhold Dirk , Schraven Burkhart , Togni Mauro 
Published: April 2009

Abstract
The genetic deletion of SKAP-HOM, an ubiquitously expressed cytosolic adapter protein, affected DC:T cell interactions reducing immune response.
The cytosolic adaptor molecule SKAP-HOM, similar to the T cell-specific homologue SKAP55, interacts directly with ADAP, and both molecules are involved in inside-out signaling. Previous studies have shown that in the absence of SKAP-HOM, antigen receptor-triggered integrin-mediated adhesion is impaired severely in B cells but not in T cells. In addition, loss of SKAP-HOM results in a less severe clinical course of EAE. DCs are the most potent APCs and express SKAP-HOM. However, the role of SKAP-HOM in DCs remains unknown. Here, we assessed whether the reduced severity of EAE observed in SKAP-HOM-deficient mice is at least partially a result of an impaired cooperation between APCs and T cells. We demonstrate that migration of LC in vivo and the spontaneous motility of BMDCs in vitro are increased in the absence of SKAP-HOM. In contrast, triggering of the integrin results in a drastic decrease of DC motility and in enhanced actin polymerization in SKAP-HOM-deficient DCs. Furthermore, the antigen-dependent conjugate formed between wild-type T cells and SKAP-HOM−/− DCs is delayed in comparison with wild-type DCs. Strikingly, fewer antigen-specific T cells are induced by immunization with SKAP-HOM−/− BMDCs as compared with wild-type BMDCs in vivo. Thus, these findings suggest that SKAP-HOM expression in DCs is required for the induction of an optimal immune response.
Sepsis-induced human lymphocyte apoptosis and cytokine production in “humanized” mice
Authors: Unsinger Jacqueline , McDonough Jacquelyn S , Shultz Leonard D , Ferguson Thomas A , Hotchkiss Richard S 
Published: April 2009

Abstract
Sepsis in mice possessing a functional human immune system causes extensive apoptotic death of human immune effector cells and increases in both pro- and anti-inflammatory human cytokines.
Sepsis is the leading cause of death in critically ill patients in the United States with over 210,000 deaths annually. One stumbling block to an effective therapy of sepsis has been the lack of a clinically relevant animal model. There are important distinctions in the mouse versus human immune system regarding the host response to invading pathogens. These differences may explain the disappointing results in many sepsis clinical trials despite the clear efficacy of these agents in mouse models of sepsis. The purpose of the present study was to develop a “humanized” mouse model of sepsis and to determine if the model recapitulated the major findings of lymphocyte apoptosis and cytokine response that exist in patients with sepsis. Two-day-old NOD-scid IL2rγnull mice received an adoptive transfer of hCD34+ hematopoietic cord blood stem cells. These mice acquired a functional human innate and adaptive immune system, as evidenced by the development of all lineages of human immune cells as well as by mounting a DTH response. Eight weeks post-transfer, mice were made septic using the highly clinical relevant CLP model of sepsis, and sepsis induced marked elevations in human pro- and anti-inflammatory cytokines as well as a dramatic increase in human T and B cell apoptosis. Collectively, these results show that the humanized mouse model recapitulates many of the classic findings in patients with sepsis. Therefore, it represents an advanced, clinically relevant model for mechanistic studies of sepsis and testing of novel therapies.
Virtual design of a novel two-stroke high-speed direct-injection diesel engine
Authors: Mattarelli E 
Published: April 2009

The paper reviews the virtual design process of an automotive high-speed direct-injection (HSDI) two-stroke diesel engine, developed at the Department of Mechanical and Civil Engineering (DIMeC) of the University of Modena and Reggio Emilia. The new concept of the engine is the tumble-supported and spray-controlled combustion system, which enables the adoption of loop scavenging without valves, and the use of a very simple and compact combustion chamber, carved in the engine head. The concept has been applied to a three-cylinder engine, with a capacity of 1050 cm3, supercharged by means of a Roots compressor and a variable geometry turbocharger. Some alternative configurations have been defined. Integrated one-dimensional and multidimensional computational fluid dynamics (CFD) simulations have been performed in order to optimize the main engine parameters, as well as to predict brake performance and emissions, in comparison with a reference four-stroke automobile diesel engine. Simulation results demonstrate the potential of the concept, which may be applied to develop a new generation of ultra-compact and clean automotive diesel engines.
Distinct Features of Angioimmunoblastic T-Cell Lymphoma With Bone Marrow Involvement
Authors: Cho Young-Uk , Chi Hyun-Sook , Park Chan-Jeoung , Jang Seongsoo , Seo Eul-Ju , Huh Jooryung 
Published: April 2009

Abstract
We retrospectively reviewed the clinical and laboratory data and bone marrow (BM) histomorphologic features in 33 angioimmunoblastic T-cell lymphoma (AITL) cases. Paraffin-embedded BM core biopsy specimens were reacted immunohistochemically with antibodies to pan–T-cell markers, CD20, CD10, CD21, and bcl-6. The frequency of BM involvement was 70% (23/33). The following features were more significant in patients with than without BM involvement: fever, hepatosplenomegaly, pleural effusion, elevated lactate dehydrogenase level, hypoalbuminemia, hyponatremia, hypocalcemia, anemia, circulating atypical cells, hypercellular marrow, and plasmacytosis in the BM. Morphologic features included nodular or interstitial infiltration in a paratrabecular distribution, periodic acid–Schiff–positive intercellular materials, mixed infiltrates of T and B cells, presence of clear cells, and blood vessel proliferation. Immunohistochemical assays revealed that CD5, bcl-6, and CD10 were useful markers of BM infiltration. Seven cases with BM involvement were interpreted as negative for lymphoma initially, mainly owing to insufficient information in nodal biopsy specimens. Several clinical and laboratory features indicate BM involvement of AITL at diagnosis. Laboratory physicians should be more familiar with BM histomorphologic and immunophenotypic characteristics suggesting AITL infiltration to make accurate diagnoses even without prior nodal biopsies.
Results of an External Proficiency Testing Exercise on Platelet Dense-Granule Deficiency Testing by Whole Mount Electron Microscopy
Authors: Hayward Catherine P.M. , Moffat Karen A. , Spitzer Ernie , Timleck Marnie , Plumhoff Elizabeth , Israels Sara J. , White James ,   on behalf of the NASCOLA Working Group on Platelet Dense Granule Deficiency
Published: April 2009

Abstract
Performance on specialized diagnostic tests for platelet disorders, including dense-granule deficiency, is rarely evaluated by external quality assessment (EQA). Members of the North American Specialized Coagulation Laboratory Association that evaluate platelet dense-granule deficiency commonly use whole-mount electron microscopy (EM) methods. This observation led us to develop a pilot EQA survey with standardized EM images and clinical samples on grids from a healthy control subject and a subject with dense-granule deficiency. The survey participants were 8 centers, including 2 with no experience in platelet whole mount EM. All participants, including inexperienced sites, correctly interpreted findings for the normal and dense-granule-deficient platelets. Among experienced sites, agreement was excellent (&gt;82%) on platelet structures to count or not count as dense granules. Participants indicated that future EQA challenges should include clinical samples on grids and standardized images. This is the first report that platelet EM can be assessed by EQA.
Touchscreen ohne Touch – Berührungslose 3D Gesten-Interaktion für den OperationssaalTouchscreen without Touch – Touchless 3D Gesture Interaction for the Operation Room
Authors: Penne Jochen , Soutschek Stefan , Stürmer Michael , Schaller Christian , Placht Simon , Kornhuber Johannes , Hornegger Joachim 
Published: April 2009

Zusammenfassung
Time-of-Flight-Kameras bieten die Möglichkeit, berührungslos in Echtzeit Distanzen zu messen. Diese technischen Möglichkeiten werden genutzt, um die dreidimensionale Zeigerichtung einer Hand relativ zu einem Monitor zu berechnen. Dadurch kann berechnet werden, wohin der Nutzer auf dem Monitor zeigt und der Mauszeiger an die entsprechende Position gesetzt werden. Durch das Heben und Senken des Daumens wird ein Klick ausgelöst. Somit werden die Basis-Funktionalitäten eines Touchscreens, ohne ihn dabei berühren zu müssen, zur Verfügung gestellt. Das berührunglose Messverfahren der Time-of-Flight-Kameras eignet sich hervorragend für den Einsatz im Operationssaal, da dort unter Sterilitätsbedingungen gearbeitet werden muss. Das vorgeschlagene Interaktionsparadigma ist wegen seiner intuitiven Nutzbarkeit auch gerade für die Nutzung durch Ärzte geeignet, was durch durchgeführte Studien bestätigt wird.
Bewertung sicherheitskritischer Systeme im OperationssaalEvaluation of Risk-Sensitive Systems in the OR
Authors: Janß Armin , Lauer Wolfgang , Radermacher Klaus 
Published: April 2009

Zusammenfassung
Im Rahmen des BMWi-geförderten Projektes INNORISK wird derzeit am Lehrstuhl für Medizintechnik der RWTH Aachen eine formal-analytische Methodik sowie ein flankierendes Softwaretool zur prospektiven Gebrauchstauglichkeitsprüfung komplexer Medizinprodukte entwickelt. Diese Module sollen die experimentelle Usability-Evaluierung sowie die Durchführung und Einhaltung des im Rahmen der europäischen Ergänzungsnorm IEC 60601-1-6 für medizinische elektrische Geräte geforderten Usability-Engineering Prozesses unterstützen. Der verfolgte modellbasierte Ansatz soll dabei die Analyse der Belastung bzw. Beanspruchung intraoperativ Tätiger sowie der hieraus resultierenden Risiken für Patient und OPTeam erleichtern. Basierend auf einem zweigeteilten Ansatz werden benutzerinteraktive Prozesssequenzen und deren möglicher Einfluss auf den Gesamtprozess bewertet. Zunächst wird eine Erweiterung der ConcurTaskTree (CTT) Methodik, eine High-Level Aufgabenanalyse, durchgeführt. Anschließend wird eine CPM-GOMS (Cognitive Perceptual Motor – Goals Operators Methods Selection Rules) Erweiterungsmethodik, eine Low-Level kognitive Aufgabenanalyse, angewendet und integriert. Ausgehend hiervon wird für kritische Prozesssequenzen eine kognitive Aufgabenanalyse unter Berücksichtigung unterschiedlicher leistungsbegrenzender Faktoren zur Bewertung der mentalen Belastung im spezifischen chirurgischen Nutzungskontext durchgeführt. Auf Basis verschiedener Fehlertaxonomien bezüglich menschlicher Fehler können dann gezielt potenzielle Risiken und Gefahren in den einzelnen Phasen der Informationsaufnahme, -verarbeitung und -ausgabe abgeleitet werden. Ziel dieses Ansatzes ist es, die Gebrauchstauglichkeit von Medizinprodukten in diesem speziellen Kontext zu verbessern und Interface-Designern sowie technischen Entwicklern methodische, softwaregestützte Analysewerkzeuge zur Erfassung inhärenter humaninduzierter Gefahrenpotentiale im Zusammenhang mit der Nutzung komplexer medizintechnischer Produkte zur Verfügung zu stellen. Kleine und mittlere Unternehmen, welche die Medizintechnikbranche prägen, sollen hierdurch im Rahmen des Zulassungsprozesses von Medizinprodukten unterstützt werden.
Überwachung von Kommunikationssatelliten – Fallstudie BenutzungsschnittstelleControlling Communication Satellits – Case Study: The User Interface
Authors: Linn Rolf 
Published: April 2009

Zusammenfassung
Für den Satellitenbetreiber SES ASTRA in Luxem burg wird vom Institut für Innovative Informatik-Anwendungen i3A der Fachhochschule Trier die Benutzungsschnittstelle eines Systems zur Leistungs messung von Kommunikations - satelliten entworfen. Wegen neuer Einsatzanforderungen, veralteter Hardware- und Softwaretechnologien und demzufolge anzupassender Nutzungsqualität soll das existierende System durch ein neues ersetzt werden. Diese Fallstudie stellt die Anwendung der DATech-Prüfverfahren für die Entwicklung und Qualitätssicherung der Benutzungsschnittstelle vor. Obwohl als ”Prüfverfahren“ bezeichnet, ist das Verfahren durchaus für Designprojekte anwendbar. In der hier beschriebenen ersten Phase wurden die Nutzungsanforderungen entwickelt, diese in Interaktionsentwurf sowie Systemoberfläche umgesetzt und ein Vorschlag für die grafische Gestaltung erarbeitet.
Blickbewegungsanalyse zur software-ergonomischen EvaluationEye Tracking Analysis for Software-Ergonomic Evaluation
Authors: Schmidt Ludger 
Published: April 2009

Zusammenfassung
Zur Bewertung der Gebrauchstauglichkeit von Mensch-Maschine-Schnittstellen bieten sich zahlreiche Methoden an, deren Ergebnisse als konstruktive Basis für die benutzungsbezogene Verbesserung herangezogen werden können. In diesem Beitrag wird die Methode der Blickbewegungsanalyse mit ihren zentralen Parametern als software-ergonomisches Evaluationsverfahren vorgestellt und beispielhaft für die Untersuchung und Bewertung einer webbasierten Buchungsoberfläche für Flugtickets verwendet. Zusätzlich zu Benutzerleistungsdaten (wie Ausführungszeiten und Fehler) stehen damit weitere verhaltensbeschreibende objektive Daten zur Verfügung, die durch in Benutzerbefragungen erhobene, subjektive software-ergonomische Bewertungen ergänzt werden. Durch diese Methodenkombination sollte auch der Frage nachgegangen werden, ob sich die subjektiven und objektiven Daten sinnvoll gegenseitig ergänzen, so dass im Ergebnis besser auf Benutzbarkeitsdefizite geschlossen werden kann. An der empirischen Untersuchung des Fallbeispiels nahmen 20 Probanden teil, die jeweils drei repräsentative Ticket-Buchungsaufgaben lösen mussten. Die Auswertung der Blickbewegungs- und Leistungsdaten sowie der verwendeten Fragebögen lieferte trotz des hohen Erprobungsgrades der Buchungsschnittstelle und ihrer Vorgängerversionen insgesamt zahlreiche Hinweise, die im Sinne einer formativen Evaluation für die Überarbeitung der Buchungsoberfläche genutzt werden konnten. Die Analyse identifizierte teilweise übereinstimmende Problembereiche, ein Teil der Defizite konnte jedoch nur anhand der Blickbewegungsdaten aufgedeckt werden.
Fiber intake predicts ghrelin levels in overweight and obese postmenopausal women
Authors: St-Pierre David H , Rabasa-Lhoret Rémi , Lavoie Marie-Ève , Karelis Antony D , Strychar Irene , Doucet Eric , Coderre Lise 
Published: April 2009

BackgroundGhrelin levels are decreased upon food intake, but the impact of specific diet-derived macronutrients on its regulation remains unclear. In addition, because of ghrelin's association with body weight regulation, it is important to understand the mechanisms regulating its levels in obese individuals.ObjectiveTo examine the effect of specific macronutrients on ghrelin levels in overweight and obese postmenopausal women.MethodsThirty-five subjects underwent a euglycemic/hyperinsulinemic clamp (EHC) to examine glucose disposal and total ghrelin (TotG) and acylated ghrelin (AG) levels. Macronutrient intake was evaluated with a 3-day food questionnaire.ResultsUnder fasting conditions, positive associations were observed between fiber intake and TotG and AG levels. Fasting AG also correlated positively with the intake of total energy, as well as monounsaturated and polyunsaturated lipids. Importantly, fiber consumption explained up to 26 and 23% of the variation in TotG and AG respectively. During the EHC, TotG levels were significantly reduced at all times, while AG was decreased at 60 min only. TotG area under the curve (AUC) values were positively associated with fiber and polyunsaturated lipid intake, while AG AUC values correlated positively with fiber, total energy, carbohydrate, and lipid intake. Interestingly, fiber intake explained up to 21% of the variation in TotG AUC, while total energy intake predicted up to 21% of the variation in the AG AUC.ConclusionThe present study suggests that fiber intake is an important regulator of ghrelin levels both in fasting and in hyperinsulinemic conditions. Overall, these results reinforce the importance of the intimate association between eating habits and gastrointestinal hormonal regulation.
Long‐acting reversible contraceptives
Authors: Fleming Charlotte F 
Published: April 2009

The majority of women use the less reliable methods of contraception.
The majority of oral contraceptive users miss two or three pills per packet.
Thinking has changed from promoting user‐dependent to user‐independent contraceptive methods.
Intrauterine devices do not cause pelvic infection or ectopic pregnancy.
There is no lower age limit for users of any long‐acting reversible contraceptives, including intrauterine devices.

Learning objectives:

To understand the advantages of user‐independent methods of contraception.
To be able to combat myths and misunderstandings relating to them.

Ethical issues:

Fraser competence should be sought whenever a new method of contraception is chosen by someone under 16 who is not involving their parents in their decision.
Some people may find the intrauterine copper device unacceptable, as one of its contraceptive actions may be to prevent an embryo from implanting.

Please cite this article as: Fleming CF. Long‐acting reversible contraceptives. The Obstetrician & Gynaecologist 2009;11:83–88.
Prenatal diagnosis and management of fetal infections
Authors: To Meekai , Kidd Michael , Maxwell Darryl 
Published: April 2009

The risks of transplacental transmission and fetal damage are pathogen‐ and gestation‐specific.
Amniocentesis is the mainstay of diagnosis of fetal infection.
Ultrasound surveillance is the primary tool for the detection of an affected fetus.
Therapeutic options are restricted to intrauterine blood transfusion in parvovirus infection and maternal antibiotic therapy in toxoplasmosis infection.

Learning objectives:

To gain an overview of prenatal diagnosis of the commonest congenital infections.
To appreciate that optimal care involves a multidisciplinary approach.

Ethical issues:

Detection of virus alone is not synonymous with fetal damage; a negative result does not completely exclude the possibility of fetal infection.
Presence or absence of sonographic markers of fetal infection may not accurately predict long‐term outcome.

Please cite this article as: To M, Kidd M, Maxwell D. Prenatal diagnosis and management of fetal infections. The Obstetrician & Gynaecologist 2009;11:108–116.
Making decisions together, or wake me up when it is over?
Authors: Leigh Bertie 
Published: April 2009

Forty years ago, doctors were told that ‘doctor knows best’ was not a defence.
Twenty years ago they realised that, in seeking consent, they had to advise of the risks involved.
The General Medical Council recently revised their guidance on consent: doctors must work in partnership with patients and not press them to accept their advice.

Learning objectives:

To be aware of the guidance from the GMC on seeking consent.
To learn about some of the major legal cases involving consent.
To be able to consider the issues involved in consent.

Ethical issues:

Doctors carry the burden of acting as distributors of scarce resources.
The duty of doctors to make decisions about treatment jointly with patients can be hard to reconcile with the duty to give clear advice.

Please cite this article as: Leigh B. Making decisions together, or wake me up when it is over? The Obstetrician & Gynaecologist 2009;11:117–121.
Dealing with conflict and aggression in obstetrics and gynaecology
Authors: Strachan Bryony K , Fuller Jo Baden 
Published: April 2009

Information points:

In a BMA survey, half of obstetricians and gynaecologists had experienced violence and aggression in the previous year.
Patients and staff have a right to be treated with respect; staff should not tolerate physical or verbal abuse.
Communication problems surrounding care and service provision are common causes of conflict.
Effective antenatal and pre‐admission planning can minimise conflict.

Learning objectives:

To understand the causes of conflict and aggression and to be aware of strategies for prevention.
To learn how to recognise potentially violent and aggressive situations and be able to manage them effectively.

Ethical issues:

Is it possible to protect oneself in an abusive situation without compromising care?
Healthcare staff have the right to work in a non‐abusive working environment.

Please cite this article as: Strachan BK, Baden Fuller J. Dealing with conflict and aggression in obstetrics and gynaecology. The Obstetrician & Gynaecologist 2009;11:122–128.
Prophylactic human papillomavirus vaccination update
Authors: Fiander Alison 
Published: April 2009

Prophylactic human papillomavirus (HPV) vaccination was implemented in the UK in 2008 for girls aged 12–13 years.
There is a ‘catch‐up’ programme for girls up to the age of 18 years.
The bivalent vaccine (Cervarix®), covering HPV 16 and 18 was chosen for the first 3 years of the UK vaccination programme.
Surveillance is essential to evaluate long‐term effectiveness and answer the remaining questions.

Learning objectives:

To be aware of the implementation of HPV vaccination in the UK.
To be aware of remaining unanswered questions and the need for surveillance.
To understand the importance of key messages for girls being vaccinated against HPV.

Ethical issues:

Will HPV vaccination of girls in the UK be acceptable to everyone?
Have the key public health messages been clearly stated and understood?
Addressing the major burden of HPV‐related neoplasia in developing countries is an ethical imperative.

Please cite this article as: Fiander A. Prophylactic human papillomavirus vaccination update. The Obstetrician & Gynaecologist 2009;11:133–135.
Molecular Characterization of the Human NANOG Protein
Authors: Chang David F. , Tsai Steven C. , Wang Xing Chao , Xia Ping , Senadheera Dinithi , Lutzko Carolyn 
Published: April 2009

Abstract
NANOG is a key transcriptional regulator of pluripotent stem cell (PSC) self-renewal. NANOG occupies promoters that are active and others that are repressed during self-renewal; however, the mechanisms by which NANOG regulates transcriptional repression and activation are unknown. We hypothesized that individual protein domains of NANOG control its interactions with both the promoters and its coregulators. We performed a detailed characterization of the functional domains in the human (h) NANOG protein, using a panel of deletion-mutant and point-mutant constructs. We determined that six amino acids in the homeodomain (136YKQVKT141) are sufficient for the nuclear localization of hNANOG. We also determined that the tryptophan-rich region (W) of hNANOG contains a CRM1-independent signal for nuclear export, suggesting a possible cellular shuttling behavior that has not been reported for hNANOG. We also show that at least four tryptophans are required for nuclear export. We also determined that similar to murine (m) NANOG, the W region of hNANOG contains a homodimerization domain. Finally, in vitro transactivation analyses identified distinct regions that enhance or diminish activity at gene promoters that are active during self-renewal. Specifically, the N-terminal region interferes with transcription and removal of this region that produced a “super-active” hNANOG with enhanced transcriptional activity. We also confirmed that the transcriptional activator in hNANOG is contained in the C-terminal region, similar to murine NANOG. In summary, this study has characterized the structure and function of hNANOG protein leading to an increased understanding of the mechanism by which hNANOG regulates both transcriptional activation and repression during PSC self-renewal.
Disclosure of potential conflicts of interest is found at the end of this article.