bluuebunny/crossref_metadata_2025 huggingface dataset:
A 10-Year Prospective Trial of a Patient Management Algorithm and Screening Examination for Highly Active Individuals with Anterior Cruciate Ligament Injury
Authors: Hurd Wendy J. , Axe Michael J. , Snyder-Mackler Lynn
Published: October 2007

Objective

To clarify the determinants of dynamic knee stability early after anterior cruciate ligament injury.

Study Design

Cohort study (diagnosis); Level of evidence, 1.

Methods

Three hundred forty-five consecutive patients who were regular participants in International Knee Documentation Committee level I/II sports before injury and had an acute isolated anterior cruciate ligament injury from the practice of a single orthopaedic surgeon underwent a screening examination including clinical measures, knee laxity, quadriceps strength, hop testing, and patient self-reported knee function a mean of 6 weeks after injury when impairments were resolved. Independent t tests were performed to evaluate differences in quadriceps strength and anterior knee laxity between potential copers and noncopers. Hierarchical regression was performed to determine the influence of quadriceps strength, preinjury activity level, and anterior knee laxity on hop test performance, as well as the influence of timed hop, crossover hop, quadriceps strength, preinjury activity level, and anterior knee laxity on self-assessed global function.

Results

Neither anterior knee laxity nor quadriceps strength differed between potential copers and noncopers. Quadriceps strength influenced hop test performance more significantly than did preinjury activity level or anterior knee laxity, but the variance accounted for by quadriceps strength was low (range, 4%–8%). Timed hop performance was the only variable that affected self-assessed global function.

Conclusion

Traditional surgical decision making based on passive anterior knee laxity and preinjury activity level is not supported by the results, as neither is a good predictor of dynamic knee stability. A battery of clinical tests that capture neuromuscular adaptations, including the timed hop test, may be useful in predicting function and guiding individualized patient management after anterior cruciate ligament injury.
Tunnel Positioning of Anteromedial and Posterolateral Bundles in Anatomic Anterior Cruciate Ligament Reconstruction
Authors: Zantop Thore , Wellmann Mathias , Fu Freddie H. , Petersen Wolf
Published: October 2007

Background

The interest in double-bundle anterior cruciate ligament (ACL) reconstructions has recently reawakened.

Hypothesis

The center of the femoral posterolateral (PL) bundle and the center of the femoral anteromedial (AM) bundle are not within the same plane and change their orientation throughout passive knee flexion. Additionally, the tibial center of the AM bundle is aligned with the anterior horn of the lateral meniscus and the center of the PL bundle lies at the recommended tibial tunnel position for single-bundle ACL reconstruction reconstruction, 7 to 9 mm anterior to the posterior cruciate ligament.

Study Design

Descriptive laboratory study.

Materials

In 20 human cadaveric knees (age range, 45–87 years) the distances from the center of the AM and PL bundle to the articular cartilage were measured. Radiographic analyses were performed using the techniques of Bernard and Hertel at the femur as well as the method by Stäubli and Rauschning at the tibia.

Results

The center of the AM bundle was at a point 5.3 mm (± 0.7) from the roof of the notch and 5.7 mm (± 0.5) from the intercondylar line. The center of the PL bundle is located at 6.5 mm from the shallow cartilage margin and 5.8 mm from the inferior cartilage margin. On the tibia, the center of the AM bundle is aligned with the anterior horn of the lateral meniscus, while the center of the PL bundle was located 11.2 mm (± 1.2) posterior and 4.1 mm (± 0.6) medial to the anterior insertion of the lateral meniscus. Radiographically, the center of the PL bundle is anterior along Blumensaat's line and lower in the femoral notch along the height of the condyles than the center of the AM bundle. At the tibia, the center of the AM bundle is at 30% and the PL bundle is located at 44% using the method of Stäubli and Rauschning.

Conclusion

The center of the femoral PL bundle is shallow and inferior to the AM bundle. On the tibia, the AM bundle lies anterior when compared with the typical single-bundle ACL tunnel that reflects the PL bundle.

Clinical Relevance

To imitate the anatomy of the intact ACL, it is mandatory to place the tunnels exactly within the femoral origin and tibial insertion of the ACL.
Accommodating Students With Disabilities in Large-Scale Testing
Authors: Bolt Sara E. , Ysseldyke Jim
Published: October 2007

Many students with disabilities are provided accommodations to enable their participation in statewide assessment programs; however, there is concern that accommodations may invalidate test results. For test administrations to be considered valid for all student groups, there must be comparable measurement across groups. This can ensure that decisions based on test results are made in a fair manner for all students. In this study, measurement comparability for two groups of accommodated students with disabilities (i.e., accommodated students with physical disabilities and accommodated students with mental disabilities) was examined using differential item functioning (DIF) analysis, in which item-level characteristics of the test for these groups were systematically compared with those for a reference group of nonaccommodated students without disabilities. A relatively large number of DIF items were identified for both accommodated disability groups, suggesting that more attention to the testing needs of students with disabilities is warranted. Suggestions for future research are provided.
Ambition, Gender, and the Judiciary
Authors: Williams Margaret S.
Published: October 2007

With the work of scholars like Fox and Lawless (2004) and Sanbonmatsu (2002), the discipline of political science began to understand individual-level explanations for women's representation in state legislatures. Such analysis, however, has not been extended to other branches of government, including state judiciaries. To examine individual-level explanations for representation on state courts, this article examines the results of a survey of Texas attorneys. The results of this research suggest that running for the judiciary is somewhat different from running for other office, and future research needs to explore the variation in ambition across types of offices.
The Speaker's Discretion
Authors: Lazarus Jeffrey , Monroe Nathan W.
Published: October 2007

House rules allow the Speaker to choose any conferees he wishes, suggesting he might use conference delegations to advance partisan goals. In practice, the Speaker nearly always selects members of the bill's jurisdictional committee(s). The authors propose a theory of conferee selection that endogenizes both partisan goals and committee participation. They argue that the Speaker's incentives lead him to appoint committee members, but he anticipates cases in which they would produce an outcome unfavorable to the majority party. In these cases, the Speaker appoints other conferees in addition to those from the jurisdictional committee, thereby “packing” the delegation in favor of the majority party position. The authors derive and test hypotheses regarding when the Speaker packs conference delegations, and what delegations look like when packed. The tests support the theory.
Sex Differences in the Acceptability of Discrimination
Authors: Kuran Timur , McCaffery Edward J.
Published: October 2007

A large telephone survey conducted after the attacks of September 11, 2001, suggests that the willingness to tolerate discrimination varies significantly across domains, with a very high tolerance of discrimination against poorly educated immigrants and a strikingly low tolerance of discrimination against the genetically disadvantaged. Regardless of domain, tolerance is greater among men than among women. A survey conducted simultaneously over the World Wide Web, using volunteer panels, replicated the phone survey results and revealed an even larger sex gap. This finding suggests that a social desirability bias leads women to overstate and men to understate their tolerance of discrimination in public.
Ideological Ambiguity and Split Ticket Voting
Authors: Karp Jeffrey A. , Garland Marshall W.
Published: October 2007

Recent research on congressional elections suggests that voters are more likely to split their votes in ideologically extreme districts. The authors suggest that in this type of context, uncertainty about candidate position rather than clarity explains the occurrence of ticket splitting. Using data from a rolling cross-section campaign survey where two incumbents competed in a predominately conservative district, the authors find that a substantial proportion of voters are likely to have difficulty identifying which congressional candidate was more conservative. Moreover, media exposure contributed to ambiguity over candidate position, which increases the likelihood of ticket splitting.
Get Safety Problems to the Surface
Authors: Lauver Kristy J. , Lester Scott W.
Published: October 2007

This study examines the relationship that employee perceptions of rewards, training, and selection have with reported and unreported employee injuries requiring doctor's attention, first aid cases, and near misses. Additionally, this study examines the relationship of selection and training with injury reporting beyond that of rewards, because reporting relationships have not previously been examined in either of these areas. Study results indicate that employee perception of training is associated with a decrease in the number of unreported injuries including doctor's attention, first aid cases, and near misses, and employee perceptions of selection are associated with a decrease in the number of unreported first aid cases. Both training and selection were related to the number of unreported injuries above and beyond the effect of rewards for safety. Implications of these findings are discussed.
An Investigation of the Effects of Psychological Contract and Organization-Based Self-Esteem on Organizational Commitment in a Sample of Permanent and Contingent Workers
Authors: Hughes Larry W. , Palmer David K.
Published: October 2007

In this cross-sectional research design, the authors explore and offer evidence of differential obligations of permanent and contingent workers to their organization. Additionally, they holistically investigate the relationships between different psychological contract obligations and two dimensions of organizational commitment. They found limited support for the hypotheses that psychological contract perceptions varied across permanent and contingent workers and levels of commitment. Additionally, they discovered that organization-based self-esteem partially mediated the relationship between psychological contract and organizational commitment. Implications for management practice, limitations of the study, and directions for future research are also offered.
Differences Between Part-Time and Full-Time Employees in the Financial Services Industry
Authors: Clinebell Sharon K. , Clinebell John M.
Published: October 2007

Although part-time employees account for approximately 17% of the workforce, how, or if, they differ from full-time employees is still unknown. This study addresses the question of whether part-time and full-time employees differ on job satisfaction, organizational commitment, job involvement, role ambiguity, role conflict, and inclusion. Additionally, the respondents were from the financial services industry, which has been underrepresented in the part-time employment studies. Part-time employees were found to have lower levels of job involvement and inclusion.
A Bully as an Archetypal Destructive Leader
Authors: Harvey Michael G. , Buckley M. Ronald , Heames Joyce T. , Zinko Robert , Brouer Robyn L. , Ferris Gerald R.
Published: October 2007

Leaders do not necessarily have the best interests of the organization in mind when they make decisions. Many times, leaders treat their own personal goals as more important in relation to the goals of the organization and frequently adopt a short-term decision horizon. Thus, leaders become destructive and make decisions for their own good at the expense of the organization. This article examines the bully as a leader and how the bully creates a dysfunctional environment where the bullied, the observer, and the organization suffer negative impact due to the decisions made by the bully. The externalities of bullying (i.e., unintended explicit and/or implicit consequences of bullying activities on the members of the organization) are discussed to highlight the importance of examining the spillover impact of bullying activities in organizations. In addition, the authors propose a method to address the negative impact of those who engage in bullying on the organizational as a whole.
Integration of Social Identities in the Self: Toward a Cognitive-Developmental Model
Authors: Amiot Catherine E. , de la Sablonnière Roxane , Terry Deborah J. , Smith Joanne R.
Published: October 2007

This article presents a model of social identity development and integration in the self. Classic intergroup theories (e.g., social identity theory, self-categorization theory) address the situational, short-term changes in social identities. Although these theories identify the contextual and environmental factors that explain situational changes in social identification, the intraindividual processes underlying developmental changes in social identities and their integration within the self remain to be identified. Relying on recent intergroup models as well as on developmental (i.e., neo-Piagetian) and social cognitive frameworks, this article proposes a four-stage model that explains the specific processes by which multiple social identities develop intraindividually and become integrated within the self over time. The factors that facilitate versus impede these identity change processes and the consequences associated with social identity integration are also presented.
Electrophoretic deposition of TiO2 and TiO2 + CeO2 coatings on type 304L stainless steel
Authors: Mudali U. Kamachi , Sridhar T. M. , Rajendran N.
Published: October 2007

Electrophoretic deposition (EPD) was employed to coat TiO2 and TiO2+CeO2 on AISI type 304L stainless steel (SS) to improve its corrosion resistance. Coatings were obtained by following three main steps, namely formation of a suspension of the charged TiO2 particles with addition of CeO2, deposition of the suspended particles on the electrode under the influence of a dc electric field, and sintering of the particulate deposit at 1073 K for 2 h in vacuum to form a dense and continuous film. The uniform deposits of TiO2 and TiO2+CeO2 formed on the surface shown good sintering characteristics and were characterised using X-ray diffraction (XRD) technique. The electrochemical investigation of the coatings in neutral chloride media was carried out to obtain open circuit potential (OCP) and potentiodynamic anodic polarisation behaviour in order to evaluate their corrosion resistance. The electrochemical parameters shifted towards noble direction for the TiO2 and CeO2+TiO2 coated specimens in comparison with uncoated type 304L SS. The addition of CeO2 to TiO2 coating brings about a decrease in passive current density and an increase in the passivation range. The effect was significant at 15 and 20% of CeO2 addition to TiO2 coating indicating the stable nature of the coatings.
Oxygen cold plasma treatment on polypropylene: Influence of process parameters on surface wettability
Authors: Sorrentino L. , Carrino L. , Napolitano G.
Published: October 2007

Polypropylene is one of the most versatile polymers. The wide range of physical properties and relative ease of processing make it an extremely attractive material capable of competing with more expensive resins in a number of demanding applications. Its key limitation is its poor adhesion towards paints. The low polarity of the molecules in polypropylene is the cause of the low surface energy of these plastics. Increasing the surface energy is one of the major purposes of pretreatment for such plastics. The cold plasma process represents a more efficient, cleaner and cheaper treatment than the flaming traditional treatment to activate polypropylene surfaces. The aim of this work has been to evaluate the influence of oxygen cold plasma parameters on wettability of polypropylene surfaces treated. The wettability aging time has been also assessed because it represents a fundamental step to plan the insertion of the plasma process inside an industrial system. A set of process variables (voltage, time and pressure) has been identified and used to carry out some experimental tests on the basis of Design of Experiment techniques. The polypropylene wettability has been quantitatively characterised by the standard procedure detailed in ASTM D724 along the aging time.
Eddy currents to control steel decarburising
Authors: Mercier D. , Chicot D. , Decoopman X. , Lesage J.
Published: October 2007

The work presented in the present paper aims at evaluating the opportunity of the eddy current method to characterise the decarburising extent which can occur during usual heat treatments of steel like austenising. The present work is based on previous studies highlighting the ability of eddy current to detect superficial defects such as cracks, pores or the possibility to corroborate its signal intensity with the mechanical microhardness modifications generated by carburising of steel. That is why eddy current is used here to systematically compare non-affected sample with the decarburised ones at different levels of decarburising. Among the techniques available to characterise the extent of decarburising, i.e. optical observations and microhardness profile, the eddy current technique provides a non-destructive method which is often required from an industrial control point of view. The results obtained show a strong correlation between the eddy current signal and the decarburised depth of the samples. As a consequence, they open realistic perspectives to characterise decarburising industrially.
Tribological behaviour of plasma immersion ion implanted AISI 304 stainless steel against polymer and ceramic counterfaces
Authors: Saklakoğlu N. , Saklakoğlu I. E. , Ceyhun V. , Ağaçhan N. , Short K. T. , Collins G. A.
Published: October 2007

Type 304 austenitic stainless steel samples were implanted with nitrogen using plasma immersion ion implantation (PIII) at different temperatures between 350 and 500°C. Treated and untreated samples have been studied by wear–friction testing, microhardness measurement and scanning electron microscopy (SEM). The experimental results indicated that the hardness and wear resistance is improved by increasing the penetration depth of nitrogen, whereas the friction coefficient is significantly increased by PIII.
Low temperature plasma surface alloying of medical grade austenitic stainless steel with carbon and nitrogen
Authors: Buhagiar J. , Dong H. , Bell T.
Published: October 2007

Low temperature surface alloying with either nitrogen (nitriding) or carbon (carburising) has been successfully employed in hardening AISI 316. However, little work has been directed towards low temperature plasma surface alloying with both nitrogen and carbon simultaneously. In addition, little or no research has been conducted on the surface modification of medical grade austenitic stainless steels, such as ASTM F138 and F1586. In the present study, plasma surface alloying treatments have been conducted on medical grade ASTM F138 and ASTM F1586 as well as on engineering grade AISI 316 for comparison. Systematic materials characterisation was carried out using optical microscopy, glow discharge optical emission spectroscopy (GDOES) and X-ray diffraction (XRD). The three stainless steels had similar response to the plasma alloying treatments. At a temperature of 425°C plasma surface alloying with both carbon and nitrogen can effectively increase the surface hardness and wear resistance of the three austenitic stainless steels without compromising the corrosion resistance of the alloy.
Influence of silicon content on microstructure and antioxidation property of SiC coating for carbon–carbon composites
Authors: Huang M. , Li K. Z. , Li H. J. , Huang J. J. , Fu Q. G.
Published: October 2007

A SiC coating for carbon–carbon composites was prepared by the pack cementation method in an argon atmosphere. The influence of the silicon content in the pack cementation powder on the microstructure and antioxidation property of SiC coatings were studied. As the silicon content's <82·4 wt-%, the as obtained coating possesses a porous structure with β-SiC phase. While the silicon content is up to 85·7 wt-%, the as prepared coating is of a dense structure consisting of β-SiC, α-SiC and Si. The thickness of the coating increases with the increase in silicon content. Oxidation test shows that the antioxidation property of the coating improves greatly as the silicon content is >82·4 wt-%.
Effect of laser formed AlN/Al2O3 films on corrosion behaviour of aluminium alloy 6013
Authors: Xu W. L. , Yue T. M. , Man H. C.
Published: October 2007

Excimer laser surface melting (LSM) was conducted on aluminium alloy 6013 with the aim of ascertaining the significance of the laser formed nitride/oxide film in providing a corrosion barrier to the alloy. Laser surface melting was performed under two different gas environments, nitrogen and air. After the laser treatment, a compact AlN and Al2O3 mixed film was formed at the top surface of the N2 treated specimens, while only Al2O3 phase was found in the film of the air treated specimens. The laser formed film of some specimens was removed using ion etching, and their corrosion behaviour was studied. The potentiodynamic polarisation measurements showed that without ion etching, the corrosion current densities of the N2 treated and the air treated specimens were three orders and one order of magnitude respectively, lower than that of the untreated parent alloy. After ion etching, the corrosion current densities of the laser treated specimens were considerably increased. The time dependence of the polarisation resistances of the ion etched and unetched specimens was also determined. Equivalent circuits were presented to describe the corrosion behaviour of the various laser treated and untreated specimens.
Feasibility study of aqueous electrolyte plasma nitriding
Authors: Roy A. , Tewari R. K. , Sharma R. C. , Shekhar R.
Published: October 2007

Over the years, developments in nitriding have been driven by the need to address environmental concerns, and reduce both energy consumption and process time. The present investigation demonstrates the feasibility of nitriding of commercial grade austenitic stainless steel, in the plasma generated during the aqueous electrolysis of 5 wt-% solution of ammonium carbonate. Treatment for 20–60 min over a temperature range of 375–480°C yields nitride case depth of 20–60 μm.
Effects of ion beam voltage on properties of indium tin oxide films prepared by ion beam sputtering
Authors: Lii D.-F. , Huang J.-L. , Jen I.-J. , Lin S.-S.
Published: October 2007

Indium tin oxide (ITO) films were deposited by ion beam sputtering under various bias voltages. The deposition rate and surface roughness increased with increasing beam voltage. The ITO films showed amorphous structure and were obviously non-stoichiometric. The carrier concentration increased with increasing beam voltage. The conductive electrons of ITO films primarily originated from the oxygen vacancies Vo. The resistivity decreased to a minimum of 3·34 × 10−4 Ω cm at 450 V. The optical transmission in the visible region decreased with increasing beam voltage. Indium tin oxide films with high electron concentration had higher optical energy gap and resulted in blue shift.
AFM study of morphological development of zinc electrodeposits
Authors: Raeissi K. , Saatchi A. , Golozar M. A. , Szpunar J. A.
Published: October 2007

Atomic force microscopy was employed successfully to evaluate the morphological development of zinc electrodeposited onto steel substrate. The surface of steel was prepared in electropolished and mechanically polished conditions. Under the same depositing conditions, different types of zinc morphology were observed. Atomic force microscopy study of deposits proposed different mechanism of zinc development. On mechanically polished surface, zinc layered crystals like arrays was developed by individual nucleation of zinc followed by non-oriented growth. Conversely, on electropolished surface, nucleation of zinc followed by oriented growth (lateral growth) was observed on some grains while on the other grains direct incorporation of atoms to the microsteps of steel followed by bunching growth of these microsteps to macrosteps was detected.
Relationship between composition, bonding constitution and microstructure in unbalanced magnetron sputtered Ti–B–N thin films
Authors: Lu Y. H. , Shen Y. G. , Li K. Y.
Published: October 2007

Two types of Ti–B–N thin films with different B contents were deposited on Si(100) at room temperature at different nitrogen flowrates. Their phase configurations and microstructures were subsequently characterised. The results indicated that the nitrogen flowrate greatly affected phase configuration and film composition. At a low nitrogen flowrate, TiN bonding was preferentially formed, accompanying with small amounts of TiB and TiB2 bonds. Formation of TiB2 bonding was accelerated with increasing B content. Nanocomposite thin films mainly consisting of nanocrystalline (nc-) TiN/amorphous (a-) TiB2 were finally formed. At a high nitrogen flowrate, TiN followed by BN was first formed, accompanying with small amounts of TiB and TiB2 bonds. Formation of BN bonding was further accelerated with increasing B content. Nanocomposite thin films mainly consisting of nc-TiN and a-BN were finally produced. The present thin films are the nanocomposite of nc-TiN embedded in the a-matrix with a dense microstructure despite of the nitrogen flowrate.
Intravenous immunoglobulins reverse acute vaso-occlusive crises in sickle cell mice through rapid inhibition of neutrophil adhesion
Authors: Chang Jungshan , Shi Patricia A. , Chiang Elaine Y. , Frenette Paul S.
Published: October 2007

Previous studies using intravital microscopy in a sickle cell disease (SCD) mouse model suggest that adherent white blood cells (WBCs) play a key role in vaso-occlusion by capturing circulating red blood cells (RBCs) in venules. Commercial intravenous immunoglobulin (IVIG) given before the inflammatory stimuli increased microcirculatory blood flow and survival. To mimic the clinical situation in which SCD patients seek medical attention after the onset of symptoms, we developed an in vivo model in which the therapeutic intervention (eg, IVIG) was administered after in the inflammatory challenge. In this setting, IVIG rapidly (< 10 minutes) reduced adherent leukocyte numbers and dramatically inhibited interactions between RBCs and WBCs, resulting in improved microcirculatory blood flow and survival of sickle cell “Berkeley” mice. Longer survival correlated positively with blood flow (P = .001) and negatively with the number of adherent leukocytes (P = .001) and RBC-WBC interactions (P = .002). Using multichannel digital fluorescence videomicroscopy, we found that IVIG affected specifically the recruitment of neutrophils. Moreover, further analyses of leukocyte behavior revealed that IVIG significantly increased rolling velocities, indicating that it alters adhesion pathways involved in slow rolling. These data suggest that the potential therapeutic benefits of IVIG in SCD crises should be evaluated in a clinical trial.
ATM kinase activity modulates Fas sensitivity through the regulation of FLIP in lymphoid cells
Authors: Stagni Venturina , di Bari Maria Giovanna , Cursi Silvia , Condò Ivano , Cencioni Maria Teresa , Testi Roberto , Lerenthal Yaniv , Cundari Enrico , Barilà Daniela
Published: October 2007

Ataxia telangiectasia (A-T) is a rare cancer-predisposing genetic disease, caused by the lack of functional ATM kinase, a major actor of the double strand brakes (DSB) DNA-damage response. A-T patients show a broad and diverse phenotype, which includes an increased rate of lymphoma and leukemia development. Fas-induced apoptosis plays a fundamental role in the homeostasis of the immune system and its defects have been associated with autoimmunity and lymphoma development. We therefore investigated the role of ATM kinase in Fas-induced apoptosis. Using A-T lymphoid cells, we could show that ATM deficiency causes resistance to Fas-induced apoptosis. A-T cells up-regulate FLIP protein levels, a well-known inhibitor of Fas-induced apoptosis. Reconstitution of ATM kinase activity was sufficient to decrease FLIP levels and to restore Fas sensitivity. Conversely, genetic and pharmacologic ATM kinase inactivation resulted in FLIP protein up-regulation and Fas resistance. Both ATM and FLIP are aberrantly regulated in Hodgkin lymphoma. Importantly, we found that reconstitution of ATM kinase activity decreases FLIP protein levels and restores Fas sensitivity in Hodgkin lymphoma–derived cells. Overall, these data identify a novel molecular mechanism through which ATM kinase may regulate the immune system homeostasis and impair lymphoma development.
Live imaging of emerging hematopoietic stem cells and early thymus colonization
Authors: Kissa Karima , Murayama Emi , Zapata Agustin , Cortés Alfonso , Perret Emmanuelle , Machu Christophe , Herbomel Philippe
Published: October 2007

We recently demonstrated in zebrafish the developmental migration of emerging hematopoietic stem cells (HSCs) that is thought to occur in mammalian embryos, from the aorta-gonad-mesonephros (AGM) area to the successive hematopoietic organs. CD41 is the earliest known molecular marker of nascent HSCs in mammalian development. In this study, we show that in CD41-green fluorescent protein (GFP) transgenic zebrafish embryos, the transgene is expressed by emerging HSCs in the AGM, allowing us for the first time to image their behavior and trace them in real time. We find that the zebrafish AGM contains no intra-aortic cell clusters, so far considered a hallmark of HSC emergence. CD41GFPlow HSCs emerge in the subaortic mesenchyme and enter the circulation not through the dorsal aorta but through the axial vein, the peculiar structure of which facilitates their intravasation. The rise in CD41-gfp expression among c-myb+ HSC precursors is asynchronous and marks their competence to leave the AGM and immediately seed the caudal hematopoietic tissue (which has a hematopoietic function analogous to that of the mammalian fetal liver). Imaging the later migration of CD41-GFP+ precursors to the nascent thymus reveals that although some reach the thymus by extravasating from the nearest vein, most travel for hours through the mesenchyme from surprisingly diverse and remote sites of extravasation.
Favorable long-term follow-up results over 6 years for response, survival, and safety with imatinib mesylate therapy in chronic-phase chronic myeloid leukemia after failure of interferon-α treatment
Authors: Hochhaus Andreas , Druker Brian , Sawyers Charles , Guilhot Francois , Schiffer Charles A. , Cortes Jorge , Niederwieser Dietger W. , Gambacorti-Passerini Carlo , Stone Richard M. , Goldman John , Fischer Thomas , O'Brien Stephen G. , Reiffers Jose J. , Mone Manisha , Krahnke Tillmann , Talpaz Moshe , Kantarjian Hagop M.
Published: October 2007

Imatinib mesylate, a targeted inhibitor of BCR-ABL tyrosine kinase, is the standard of care for chronic myeloid leukemia (CML). A phase 2 trial of imatinib in late chronic-phase (CP) CML after interferon-α (IFNα) failure enrolled 532 patients, 454 with a confirmed diagnosis of CP CML. Median time from diagnosis was 34 months; median duration of imatinib treatment was 65 months. Cumulative best rates of major cytogenetic response (MCyR) and complete cytogenetic response (CCyR) were 67% and 57%, respectively. At the 5-year landmark, 184 (41%) of the 454 patients are in CCyR. At more than 6 years, 199 (44%) of the 454 patients remain on imatinib. Most responses occurred within 12 months of starting imatinib; however, some patients achieved initial MCyR and CCyR more than 5 years after imatinib initiation. Estimated rates of freedom from progression to accelerated phase (AP) and blastic phase (BP) and overall survival at 6 years were 61% and 76%, respectively. Both freedom from progression to AP/BP and overall survival (OS) were associated with cytogenetic response level at 12 months. No increase in rates of serious adverse events was observed with continuous use of imatinib for up to 6.5 years, compared with earlier time points. Imatinib continues to be an effective and safe therapy for patients with CP CML after failure of IFN.
All primitive and definitive hematopoietic progenitor cells emerging before E10 in the mouse embryo are products of the yolk sac
Authors: Lux Christopher T. , Yoshimoto Momoko , McGrath Kathleen , Conway Simon J. , Palis James , Yoder Mervin C.
Published: October 2007

The relative contribution of yolk sac (YS)–derived cells to the circulating definitive hematopoietic progenitor cell (HPC) pool that seeds the fetal liver remains controversial due to the presence of systemic circulation and the onset of hematopoiesis within the embryo proper (EP) before liver seeding. Ncx1−/− embryos fail to initiate a heartbeat on embryonic day (E) 8.25, but continue to develop through E10. We detected normal numbers of primitive erythroid progenitors in Ncx1−/− versus wild type (WT) YS, but primitive erythroblasts did not circulate in the Ncx1−/− EP. While there was no significant difference in the number of definitive HPCs in Ncx1−/− versus WT YS through E9.5, the Ncx1−/− EP was nearly devoid of HPCs. Thus, primitive erythroblasts and essentially all definitive HPCs destined to initially seed the fetal liver after E9.5 are generated in the YS between E7.0-E9.5 and are redistributed into the EP via the systemic circulation.
LIF promotes neurogenesis and maintains neural precursors in cell populations derived from spiral ganglion stem cells
Authors: Oshima Kazuo , Teo Dawn Tju Wei , Senn Pascal , Starlinger Veronika , Heller Stefan
Published: October 2007

Background

Stem cells with the ability to form clonal floating colonies (spheres) were recently isolated from the neonatal murine spiral ganglion. To further examine the features of inner ear-derived neural stem cells and their derivatives, we investigated the effects of leukemia inhibitory factor (LIF), a neurokine that has been shown to promote self-renewal of other neural stem cells and to affect neural and glial cell differentiation.

Results

LIF-treatment led to a dose-dependent increase of the number of neurons and glial cells in cultures of sphere-derived cells. Based on the detection of developmental and progenitor cell markers that are maintained in LIF-treated cultures and the increase of cycling nestin-positive progenitors, we propose that LIF maintains a pool of neural progenitor cells. We further provide evidence that LIF increases the number of nestin-positive progenitor cells directly in a cell cycle-independent fashion, which we interpret as an acceleration of neurogenesis in sphere-derived progenitors. This effect is further enhanced by an anti-apoptotic action of LIF. Finally, LIF and the neurotrophins BDNF and NT3 additively promote survival of stem cell-derived neurons.

Conclusion

Our results implicate LIF as a powerful tool to control neural differentiation and maintenance of stem cell-derived murine spiral ganglion neuron precursors. This finding could be relevant in cell replacement studies with animal models featuring spiral ganglion neuron degeneration. The additive effect of the combination of LIF and BDNF/NT3 on stem cell-derived neuronal survival is similar to their effect on primary spiral ganglion neurons, which puts forward spiral ganglion-derived neurospheres as an in vitro model system to study aspects of auditory neuron development.
Comparative gene expression profiling in two congenic mouse strains following Bordetella pertussis infection
Authors: Banus Sander , Vandebriel Rob J , Pennings Jeroen LA , Gremmer Eric R , Wester Piet W , van Kranen Henk J , Breit Timo M , Demant Peter , Mooi Frits R , Hoebee Barbara , Kimman Tjeerd G
Published: October 2007

Background

Susceptibility toBordetella pertussisinfection varies widely. These differences can partly be explained by genetic host factors. HcB-28 mice are more resistant toB. pertussisinfection than C3H mice, which could partially be ascribed to theB.pertussis susceptibility locus-1(Bps1) on chromosome 12. The presence of C57BL/10 genome on this locus instead of C3H genome resulted in a decreased number of bacteria in the lung. To further elucidate the role of host genetic factors, in particular in theBps1locus, inB. pertussisinfection, and to identify candidate genes within in this region, we compared expression profiles in the lungs of the C3H and HcB-28 mouse strains followingB. pertussisinoculation. Twelve and a half percent of the genomes of these mice are from a different genetic background.

Results

UponB. pertussisinoculation 2,353 genes were differentially expressed in the lungs of both mouse strains. Two hundred and six genes were differentially expressed between the two mouse strains, but, remarkably, none of these were up- or down-regulated uponB. pertussisinfection. Of these 206 genes, 17 were located in theBps1region. Eight of these genes, which showed a strong difference in gene expression between the two mouse strains, map to the immunoglobulin heavy chain complex (Igh).

Conclusion

Gene expression changes uponB. pertussisinfection are highly identical between the two mouse strains despite the differences in the course ofB. pertussisinfection. Because the genes that were differentially regulated between the mouse strains only showed differences in expression before infection, it appears likely that such intrinsic differences in gene regulation are involved in determining differences in susceptibility toB. pertussisinfection. Alternatively, such genetic differences in susceptibility may be explained by genes that are not differentially regulated between these two mouse strains. Genes in theIghcomplex, among whichIgh-1a/b, are likely candidates to explain differences in susceptibility toB. pertussis. Thus, by microarray analysis we significantly reduced the number of candidate susceptibility genes within theBps1locus. Further work should establish the role of theIghcomplex inB. pertussisinfection.
Expression of NDRG2 is down-regulated in high-risk adenomas and colorectal carcinoma
Authors: Lorentzen Anders , Vogel Lotte K , Lewinsky Rikke H , Sæbø Mona , Skjelbred Camilla F , Godiksen Sine , Hoff Geir , Tveit Kjell M , Lothe Inger Marie Bowitz , Ikdahl Tone , Kure Elin H , Mitchelmore Cathy
Published: October 2007

Background

It has recently been shown that NDRG2 mRNA is down-regulated or undetectable in several human cancers and cancer cell-lines. Although the function of NDRG2 is unknown, high NDRG2 expression correlates with improved prognosis in high-grade gliomas. The aim of this study has been to examine NDRG2 mRNA expression in colon cancer. By examining affected and normal tissue from individuals with colorectal adenomas and carcinomas, as well as in healthy individuals, we aim to determine whether and at which stages NDRG2 down-regulation occurs during colonic carcinogenesis.

Methods

Using quantitative RT-PCR, we have determined the mRNA levels for NDRG2 in low-risk (n = 15) and high-risk adenomas (n = 57), colorectal carcinomas (n = 50) and corresponding normal tissue, as well as control tissue from healthy individuals (n = 15). NDRG2 levels were normalised to β-actin.

Results

NDRG2 mRNA levels were lower in colorectal carcinomas compared to normal tissue from the control group (p < 0.001). When comparing adenomas/carcinomas with adjacent normal tissue from the same individual, NDRG2 expression levels were significantly reduced in both high-risk adenoma (p < 0.001) and in colorectal carcinoma (p < 0.001). There was a trend for NDRG2 levels to decrease with increasing Dukes' stage (p < 0.05).

Conclusion

Our results demonstrate that expression of NDRG2 is down-regulated at a late stage during colorectal carcinogensis. Future studies are needed to address whether NDRG2 down-regulation is a cause or consequence of the progression of colorectal adenomas to carcinoma.
Comparisons of predictors for typhoid and paratyphoid fever in Kolkata, India
Authors: Sur Dipika , Ali Mohammad , von Seidlein Lorenz , Manna Byomkesh , Deen Jacqueline L , Acosta Camilo J , Clemens John D , Bhattacharya Sujit K
Published: October 2007

Background:

Exposure of the individual to contaminated food or water correlates closely with the risk for enteric fever. Since public health interventions such as water improvement or vaccination campaigns are implemented for groups of individuals we were interested whether risk factors not only for the individual but for households, neighbourhoods and larger areas can be recognised?

Methods:

We conducted a large enteric fever surveillance study and analyzed factors which correlate with enteric fever on an individual level and factors associated with high and low risk areas with enteric fever incidence. Individual level data were linked to a population based geographic information systems. Individual and household level variables were fitted in Generalized Estimating Equations (GEE) with the logit link function to take into account the likelihood that household factors correlated within household members.

Results:

Over a 12-month period 80 typhoid fever cases and 47 paratyphoid fever cases were detected among 56,946 residents in two bustees (slums) of Kolkata, India. The incidence of paratyphoid fever was lower (0.8/1000/year), and the mean age of paratyphoid patients was older (17.1 years) than for typhoid fever (incidence 1.4/1000/year, mean age 14.7 years). Residents in areas with a high risk for typhoid fever had lower literacy rates and economic status, bigger household size, and resided closer to waterbodies and study treatment centers than residents in low risk areas.

Conclusion:

There was a close correlation between the characteristics detected based on individual cases and characteristics associated with high incidence areas. Because the comparison of risk factors of populations living in high versus low risk areas is statistically very powerful this methodology holds promise to detect risk factors associated with diseases using geographic information systems.
All-cause mortality and risk factors in a cohort of retired military male veterans, Xi'an, China: an 18-year follow up study
Authors: Sai Xiao Y , He Yao , Men Ke , Wang Bo , Huang Jiu Y , Shi Qiu L , Zhang Lei , Li Liang S , Choi Bernard CK , Yan Yong P
Published: October 2007

Background

Risk factors of all-cause mortality have not been reported in Chinese retired military veterans. The objective of the study was to examine the risk factors and proportional mortality in a Chinese retired military male cohort.

Methods

A total of 1268 retired military men aged 55 or older were examined physically and interviewed using a standard questionnaire in 1987. The cohort was followed up every two years and the study censored date was June30, 2005 with a follow-up of up to 18 years. Death certificates were obtained from hospitals and verified by two senior doctors. Data were entered (double entry) by Foxbase, and analysis was carried out by SAS for Windows 8.2. Multivariate Cox proportional hazard regression model was used to compute hazard ratio (HR) and 95% confidence interval (CI).

Results

The total person-years of follow-up was 18766.28. Of the initial cohort of 1268 men, 491 had died, 748 were alive and 29 were lost to follow up. Adjusted mortality (adjusted for age, blood pressure, body mass index, cholesterol, triglycerides, alcohol, exercise, and existing disease) was 2,616 per 100,000 person years. The proportional mortality of cancer, vascular disease and Chronic Obstructive Pulmonary Disease (COPD) were 39.71%, 28.10% and 16.90% respectively. Multivariate analysis showed that age, cigarettes per day, systolic blood pressure, triglyceride, family history of diseases (hypertension, stroke and cancer), existing diseases (stroke, diabetes and cancer), body mass index, and age of starting smoking were associated with all-cause mortality, HR (95%CI) was1.083(1.062–1.104), 1.026(1.013–1.039), 1.009(1.003–1.015), 1.002(1.001–1.003), 1.330(1.005–1.759), 1.330(1.005–1.759), 1.444(1.103–1.890), 2.237(1.244–4.022), 1.462(1.042–2.051), 2.079(1.051–4.115), 0.963(0.931–0.996)and 0.988(0.978–0.999)respectively. Compared with never-smokers, current smokers had increased risks of total mortality [HR 1.369(1.083–1.731)], CHD [HR 1.805 (1.022–3.188)], and lung cancer [HR 2.939 (1.311–6.585)].

Conclusion

The three leading causes of diseases were cancer, CHD and stroke, and COPD. Aging, cigarette smoking, high systolic blood pressure, high triglyceride, family history of cancer, hypertension and stroke, existing cases recovering from stroke, diabetes and cancer, underweight, younger age of smoking were risk factors for all-cause mortality. Quitting cigarette smoking, maintaining normal blood pressure, triglyceride and weight are effect control strategies to prevent premature mortality in this military cohort.
The binding site for neohesperidin dihydrochalcone at the human sweet taste receptor
Authors: Winnig Marcel , Bufe Bernd , Kratochwil Nicole A , Slack Jay P , Meyerhof Wolfgang
Published: October 2007

Background

Differences in sweet taste perception among species depend on structural variations of the sweet taste receptor. The commercially used isovanillyl sweetener neohesperidin dihydrochalcone activates the human but not the rat sweet receptor TAS1R2+TAS1R3. Analysis of interspecies combinations and chimeras of rat and human TAS1R2+TAS1R3 suggested that the heptahelical domain of human TAS1R3 is crucial for the activation of the sweet receptor by neohesperidin dihydrochalcone.

Results

By mutational analysis combined with functional studies and molecular modeling we identified a set of different amino acid residues within the heptahelical domain of human TAS1R3 that forms the neohesperidin dihydrochalcone binding pocket. Sixteen amino acid residues in the transmembrane domains 2 to 7 and one in the extracellular loop 2 of hTAS1R3 influenced the receptor's response to neohesperidin dihydrochalcone. Some of these seventeen residues are also part of the binding sites for the sweetener cyclamate or the sweet taste inhibitor lactisole. In line with this observation, lactisole inhibited activation of the sweet receptor by neohesperidin dihydrochalcone and cyclamate competitively, whereas receptor activation by aspartame, a sweetener known to bind to the N-terminal domain of TAS1R2, was allosterically inhibited. Seven of the amino acid positions crucial for activation of hTAS1R2+hTAS1R3 by neohesperidin dihydrochalcone are thought to play a role in the binding of allosteric modulators of other class C GPCRs, further supporting our model of the neohesperidin dihydrochalcone pharmacophore.

Conclusion

From our data we conclude that we identified the neohesperidin dihydrochalcone binding site at the human sweet taste receptor, which overlaps with those for the sweetener cyclamate and the sweet taste inhibitor lactisole. This readily delivers a molecular explanation of our finding that lactisole is a competitive inhibitor of the receptor activation by neohesperidin dihydrochalcone and cyclamate. Some of the amino acid positions crucial for activation of hTAS1R2+hTAS1R3 by neohesperidin dihydrochalcone are involved in the binding of allosteric modulators in other class C GPCRs, suggesting a general role of these amino acid positions in allosterism and pointing to a common architecture of the heptahelical domains of class C GPCRs.