bluuebunny/crossref_metadata_2025 huggingface dataset:
Actin Crosslinking Toxins of Gram-Negative Bacteria
Authors: Satchell Karla J.  F.
Published: December 2009

Actin crosslinking toxins produced by Gram-negative bacteria represent a small but unique class of bacterial protein toxins. For each of these toxins, a discrete actin crosslinking domain (ACD) that is a distant member of the ATP-dependent glutamine synthetase family of protein ligases is translocated to the eukaryotic cell cytosol. This domain then incorporates a glutamate-lysine crosslink between actin monomers, resulting in destruction of the actin cytoskeleton. Recent studies argue that the function of these toxins during infection is not destruction of epithelial layers, but rather may specifically target phagocytic cells to promote survival of bacteria after the onset of innate immune defenses. This review will summarize key experiments performed over the past 10 years to reveal the function of these toxins.
Determination of the Biological Activity and Structure Activity Relationships of Drugs Based on the Highly Cytotoxic Duocarmycins and CC-1065
Authors: Tietze Lutz F. , Krewer Birgit , Von Hof J. Marian , Frauendorf Holm , Schuberth Ingrid
Published: December 2009

The natural antibiotics CC-1065 and the duocarmycins are highly cytotoxic compounds which however are not suitable for cancer therapy due to their general toxicity. We have developed glycosidic prodrugs of seco-analogues of these antibiotics for a selective cancer therapy using conjugates of glycohydrolases and tumour-selective monoclonal antibodies for the liberation of the drugs from the prodrugs predominantly at the tumour site. For the determination of structure activity relationships of the different seco-drugs, experiments addressing their interaction with synthetic DNA were performed. Using electrospray mass spectrometry and high performance liquid chromatography, the experiments revealed a correlation of the stability of these drugs with their cytotoxicity in cell culture investigations. Furthermore, it was shown that the drugs bind to AT-rich regions of double-stranded DNA and the more cytotoxic drugs induce DNA fragmentation at room temperature in several of the selected DNA double-strands. Finally, an explanation for the very high cytotoxicity of CC-1065, the duocarmycins and analogous drugs is given.
N-alkyl-N-(phosphonoethyl) substituted (meth)acrylamides – new adhesive monomers for self-etching self-priming one part dental adhesive
Authors: Klee Joachim E , Lehmann Uwe
Published: December 2009

Novel N-alkyl-N-(phosphonoethyl) substituted mono-, bis- and tris(meth)acrylamides 3 were synthesized by two different three-step reactions and characterized by IR, 1H NMR and 13C NMR spectroscopy as well as refractive index and viscosity. The phosphonoethyl substituted (meth)acrylamide monomers show improved hydrolytic stability compared to carboxylic esters. The highest stability was found for the phosphonoethyl substituted acrylamide monomers. Acrylamides have a larger polymerization enthalpy ranging from −50 to −70 kJ·mol−1 per double bond compared to methacrylamides which show −8.57 to −25.1 kJ·mol−1 per double bond. Depending on their structure (meth)acrylamides 3 exhibit an adhesion to enamel and dentin up to 19.5 MPa. The monomer 3c shows the highest adhesion values to both substrates, namely 15.3 ± 3.4 MPa to enamel and 18.5 ± 2.3 MPa to dentin.
Myocardial Left Ventricular Dysfunction in Patients with Systemic Lupus Erythematosus: New Insights from Tissue Doppler and Strain Imaging
Authors: BUSS SEBASTIAN J. , WOLF DAVID , KOROSOGLOU GRIGORIOS , MAX REGINA , WEISS CELINE S. , FISCHER CHRISTIAN , SCHELLBERG DIETER , ZUGCK CHRISTIAN , KUECHERER HELMUT F. , LORENZ HANNS-MARTIN , KATUS HUGO A. , HARDT STEFAN E. , HANSEN ALEXANDER
Published: December 2009

Objective.

Systemic lupus erythematosus (SLE) is associated with high cardiovascular morbidity and mortality. Cardiovascular involvement is frequently underestimated by routine imaging techniques. Our aim was to determine if new echocardiographic imaging modalities like tissue Doppler (TDI), strain rate (SRR), and strain (SRI) imaging detect abnormalities in left ventricular (LV) function in asymptomatic patients with SLE.

Methods.

Sixty-seven young patients with SLE (mean age 42 ± 10 yrs) without typical symptoms or signs of heart failure or angina, and a matched healthy control group (n = 40), underwent standard transthoracic echocardiography, TDI, SRR, and SRI imaging of the LV as well as assessment of disease characteristics.

Results.

Despite findings within the normal range on routine standard 2-dimensional echocardiography, SLE was associated with significantly impaired systolic and diastolic myocardial velocities of the LV measured by TDI [mean global TDI: systolic (s): 2.9 ± 0.9 vs 3.9 ± 0.7 cm/s, p < 0.05; early (e): 4.3 ± 1.5 vs 6.3 ± 1.3 cm/s, p < 0.05; late (a): 2.9 ± 0.8 vs 3.4 ± 0.8 cm/s, p < 0.05; values ± SD); SRR (s: −0.8 ± 0.1 vs −1.1 ± 0.1 s−1; e: 1.1 ± 0.2 vs 1.6 ± 0.3 s−1; a: 0.7 ± 0.1 vs 1.0 ± 0.2 s−1; all p < 0.05); and SR (−15.11 ± 2.2% vs −19.7 ± 1.9%; p < 0.05) compared to the control group. Further, elevated disease activity, measured with the ECLAM and the SLEDAI score, resulted in significantly lower values for LV longitudinal function measured by SRR and SR, but not by TDI.

Conclusion.

SLE is associated with a significant impairment of systolic and diastolic LV longitudinal function in patients without cardiac symptoms. New imaging modalities provide earlier insight into cardiovascular involvement in SLE and seem to be superior to standard echocardiography to detect subclinical myocardial disease.
Bone Marrow Edema Is the Most Specific Finding for Rheumatoid Arthritis (RA) on Noncontrast Magnetic Resonance Imaging of the Hands and Wrists: A Comparison of Patients with RA and Healthy Controls
Authors: OLECH EWA , CRUES JOHN V. , YOCUM DAVID E. , MERRILL JOAN T.
Published: December 2009

Objective.

To evaluate the sensitivity and specificity of magnetic resonance imaging (MRI) in detecting erosions, bone edema, and synovitis in the metacarpophalangeal and wrist joints for rheumatoid arthritis (RA).

Methods.

MRI scans of bilateral hands and wrists of 40 healthy subjects and 40 RA patients were performed using 0.2 T extremity-MRI and read blindly using a modified RA MRI (RAMRIS) system (no contrast injection, imaging in 1 plane only). To determine interreader reliability, images of 10 randomly selected subjects were read independently by a musculoskeletal radiologist.

Results.

A total of 3360 bones were evaluated. Patients with RA had significantly more erosions as well as higher scores for bone edema and synovitis than healthy subjects. Age had a significant effect on the number of erosions in both groups. However, when disease duration was factored in, age became insignificant in RA patients. Erosion number correlated with positive rheumatoid factor and higher C-reactive protein values. The intraclass correlation coefficient between the 2 readers was 0.76 for individual joints and 0.88 for total scores. When having a single erosion was used as a positive test for RA, the sensitivity of this test was 90%, but the specificity was only 35%. Presence of bone edema provided 65% sensitivity and 82.5% specificity. Eliminating the lunate from scoring for bone edema increased the specificity to 87.5% while decreasing the sensitivity to 62.5%.

Conclusion.

While MRI is a highly sensitive tool for identifying and tracking the progression of erosions, erosions detected by MRI with measures commonly used in a rheumatologist’s office (no contrast, imaging in 1 plane) provide low specificity for RA. Bone marrow edema is the most specific MRI lesion for RA in this setting.
Interleukin 6 (IL-6) Deficiency Delays Lupus Nephritis in MRL-FaslprMice: The IL-6 Pathway as a New Therapeutic Target in Treatment of Autoimmune Kidney Disease in Systemic Lupus Erythematosus
Authors: CASH HANNES , RELLE MANFRED , MENKE JULIA , BROCHHAUSEN CHRISTOPH , JONES SIMON A. , TOPLEY NICHOLAS , GALLE PETER R. , SCHWARTING ANDREAS
Published: December 2009

Objective.

To investigate the pathophysiological effect of interleukin 6 (IL-6) on lupus nephritis in MRL-Faslprmice.

Methods.

We generated IL-6-deficient MRL-Faslprmice using a backcross/intercross breeding scheme. Renal pathology was evaluated using immunohistochemistry detection for macrophages, lymphocytes, vascular cell adhesion molecule-1 (VCAM-1), and TUNEL (terminal deoxynucleotide transferase-mediated dUTP nick end-labeling) for apoptotic cells, and renal IgG and C3 deposition by immunofluorescence staining. Expression of inflammatory markers in the spleen was analyzed by quantitative real-time reverse transcription-polymerase chain reaction. Serum cytokine concentrations were detected by FACS analysis.

Results.

IL-6 deficiency was highly effective in prolonging survival and ameliorating the clinical, immunological, and histological indicators of murine systemic lupus erythematosus. During the study period of 6 months, MRL-FaslprIL-6 −/− mice showed delayed onset of proteinuria and hematuria compared to IL-6-intact control mice. Survival rate was 100% in IL-6-deficient MRL-Faslprmice and 25% in the control group at 6 months of age. The absence of IL-6 resulted in significant reduction of infiltrating macrophages in the kidney (p < 0.05), a decrease in renal IgG and C3 deposition, and a reduction of CD4+ and CD8+ lymphocytes. The parenchymal adhesion molecule VCAM-1 was found to be downregulated in kidneys of MRL-FaslprIL-6 −/− compared to IL-6-intact mice. We found elevated serum levels of IL-10 and interferon-γ in IL-6-deficient mice, while splenic mRNA showed an overall downregulation of immunoregulatory genes.

Conclusion.

IL-6 is a strong promoter of lupus nephritis and may be a promising new therapeutic target in the treatment of human lupus nephritis.
Risk Factors for Clinical Coronary Heart Disease in Systemic Lupus Erythematosus: The Lupus and Atherosclerosis Evaluation of Risk (LASER) Study
Authors: HAQUE SAHENA , GORDON CAROLINE , ISENBERG DAVID , RAHMAN ANISUR , LANYON PETER , BELL AUBREY , EMERY PAUL , McHUGH NEIL , TEH LEE SUAN , SCOTT DAVID G.I. , AKIL MOHAMED , NAZ SOPHIA , ANDREWS JACQUELINE , GRIFFITHS BRIDGET , HARRIS HELEN , YOUSSEF HAZEM , McLAREN JOHN , TOESCU VERONICA , DEVAKUMAR VINODH , TEIR JAMAL , BRUCE IAN N.
Published: December 2009

Objective.

Accelerated atherosclerosis and premature coronary heart disease (CHD) are recognized complications of systemic lupus erythematosus (SLE), but the exact etiology remains unclear and is likely to be multifactorial. We hypothesized that SLE patients with CHD have increased exposure to traditional risk factors as well as differing disease phenotype and therapy-related factors compared to SLE patients free of CHD. Our aim was to examine risk factors for development of clinical CHD in SLE in the clinical setting.

Methods.

In a UK-wide multicenter retrospective case-control study we recruited 53 SLE patients with verified clinical CHD (myocardial infarction or angina pectoris) and 96 SLE patients without clinical CHD. Controls were recruited from the same center as the case and matched by disease duration. Charts were reviewed up to time of event for cases, or the same “dummy-date” in controls.

Results.

SLE patients with clinical CHD were older at the time of event [mean (SD) 53 (10) vs 42 (10) yrs; p < 0.001], more likely to be male [11 (20%) vs 3 (7%); p < 0.001], and had more exposure to all classic CHD risk factors compared to SLE patients without clinical CHD. They were also more likely to have been treated with corticosteroids (OR 2.46; 95% CI 1.03, 5.88) and azathioprine (OR 2.33; 95% CI 1.16, 4.67) and to have evidence of damage on the pre-event SLICC damage index (SDI) (OR 2.20; 95% CI 1.09, 4.44). There was no difference between groups with regard to clinical organ involvement or autoantibody profile.

Conclusion.

Our study highlights the need for clinical vigilance to identify modifiable risk factors in the clinical setting and in particular with male patients. The pattern of organ involvement did not differ in SLE patients with CHD events. However, the higher pre-event SDI, azathioprine exposure, and pattern of damage items (disease-related rather than therapy-related) in cases suggests that a persistent active lupus phenotype contributes to CHD risk. In this regard, corticosteroids and azathioprine may not control disease well enough to prevent CHD. Clinical trials are needed to determine whether classic risk factor modification will have a role in primary prevention of CHD in SLE patients and whether new therapies that control disease activity can better reduce CHD risk.
Fyn and CD70 Expression in CD4+ T Cells from Patients with Systemic Lupus Erythematosus
Authors: KOZLOWSKA ANNA , HRYCAJ PAWEL , LACKI JAN K. , JAGODZINSKI PAWEL P.
Published: December 2009

Objective.

CD4+ T cells from patients with systemic lupus erythematosus (SLE) display defective function that contributes to abnormal activation of B cells and autoantibody production.

Methods.

We compared the transcript and protein levels of Fyn and CD70 in CD4+ T cells from patients with SLE (n = 41) and healthy individuals (n = 34). The CD4+ T cells were isolated by positive biomagnetic separation technique. The quantitative analysis of messenger RNA was performed by reverse transcription and real-time quantitative PCR. The protein contents in the CD4+ T cells were determined by Western blotting analysis.

Results.

We observed significantly higher levels of Fyn (p = 0.03) and CD70 (p = 0.029) transcripts in SLE CD4+ T cells than in controls. There was a significant increase in CD70 protein levels (p < 0.0001), but not Fyn protein levels (p = 0.081) in CD4+ T cells from patients with SLE compared to healthy individuals. In the group with high disease activity [SLE Disease Activity Index (SLEDAI) ≥ 9], we observed a significantly higher Fyn protein content than in controls (p = 0.030). There was no correlation between Fyn and CD70 protein levels in SLE CD4+ T cells and disease activity as expressed in the SLEDAI scale.

Conclusion.

We confirmed previous observations of higher expression of CD70 in CD4+ T cells from patients with SLE. Our findings suggest that increased Fyn protein content in CD4+ T cells can be associated with high SLE disease activity.
Assessment of Advanced Practice Palliative Care Nursing Competencies in Nurse Practitioner Students: Implications for the Integration of ELNEC Curricular Modules
Authors: Shea Joyce , Grossman Sheila , Wallace Meredith , Lange Jean
Published: December 2009

Advanced practice nurses (APRNs) have key roles in the care of patients who are nearing death and those living with a disabling chronic disease. This article describes a mixed-method formative assessment of 36 graduate nursing students' knowledge about and attitudes toward palliative care preliminary to curricular integration of the End-of-Life Nursing Education Consortium (ELNEC) graduate core modules. Students' knowledge about palliative care was assessed using the 106-item ELNEC examination. In addition, qualitative data were gathered regarding students' definitions of palliative care, the role of the APRN in palliative care, and their definitions of a “good” and “bad” death. Results revealed students' limited knowledge about palliative care. Qualitative findings indicated that most students exclusively linked palliative care with end-of-life care and believed that the treatment they provide should have the goal of prolonging life over maintaining quality of life. Implications for curriculum design, advanced practice role development, and collaboration with community health partners are discussed.
The Development of the Next Generation of Nurse Leaders
Authors: Aduddell Kathie A. , Dorman Genie E.
Published: December 2009

This article explains the development of a value-added leadership focus to a graduate nursing program. With the changes to and complexity within the health care system, advanced practice nurses need academic preparation in advanced care management of populations and leadership competencies. Strategic environmental scanning suggested that some revisions could better prepare future nurse leaders. Through literature review and focus groups, faculty's analysis provided evidence for development of a different kind of advanced practice nurse. This process led to a graduate program that prepares nurse leaders who are competent in the clinical settings and leadership roles of today's health care organizations. The 40-semester hour program allows flexibility for minimum career disruption and a choice of tracks to accommodate individuals' educational needs. Grounded in practicum experiences and guided by health care theory, policy, and research, graduates possess the knowledge and competencies to assume the advanced leadership roles required in future health care systems.
The Professional Practice Knowledge of Nurse Preceptors
Authors: Paton Brenda I.
Published: December 2009

Significant research has been conducted and disseminated on preceptorship as an essential component in teaching and evaluating student learning in the final clinical practicum. The preceptorship triad—formally defined as an equilateral relationship among a nurse preceptor, faculty member, and undergraduate nursing student—overlooks the contextual challenges preceptors encounter. Preceptors develop relationships in the clinical setting to enhance teaching, and more importantly, to ensure student practice reflects the depth of clinical reasoning and skill acquisition necessary for safe and competent practice. Using descriptive surveys and qualitative focus groups, a research collaborative among academia, practice, and professional regulating bodies was established in southern Alberta, Canada, to research the types of knowledge nurses acquire and integrate to successfully assess, evaluate, and teach undergraduate nursing students in the clinical environment. This article describes the research findings and highlights the professional practice knowledge of nurse preceptors.
Partnering with Your Library to Strengthen Nursing Research
Authors: Hallyburton Ann , John Barbara St.
Published: December 2009

Nurses must know how to locate and evaluate health information to optimize their professional practice. However, much of the information available online and in print lacks credibility, and navigating professional research databases can prove complex. As more nursing students and nurse educators move from centralized, brick-and-mortar campuses to satellite locations and online courses, the need for adaptable library services becomes pronounced. This article describes a program that serves decentralized nursing students and nurse educators. Relationship building, one-to-one contact, and flexibility are program hallmarks. Services provided by the program and evaluation methods are discussed, and ways of building collaboration are recommended.
Evidence of Cross-boundary Use and Reuse of Digital Educational Resources
Authors: Vuorikari Riina , Koper Rob
Published: December 2009

In this study an investigation using log-files of teachersâ?? Collections of educational resources in two different platforms was conducted. The goal was to find empirical evidence from the field that teachers use and reuse learning resources that are in a language other than their mother tongue and originate from different countries than they do, for this, the term cross-boundary use of learning resources is used. In both contexts behavioural evidence was found that cross-boundary use and reuse takes place, and it was shown that it correlates with the general use and reuse trends. Moreover, it was found that cross-boundary reuse, when compared to 20% of general reuse, was notably less (37% to 55% of it). The motivation to study cross-boundary use and reuse is to set a baseline for future studies, and to understand how it can be supported and enhanced in the future.
Use of Information and Communication Technology (ICT) for Effective Open and Distant Learning (ODL)
Authors: Shah Attaullah , Khan Salimaullah
Published: December 2009

Allama Iqbal Open University (AIOU), Pakistan is one of the sixteen mega-open universities in the world, providing education opportunities to about one million students in Pakistan and the Middle East, from elementary level to doctoral level. The University has been facing quality issues in Open and Distance Learning (ODL) education, mainly due to the poor interaction between tutors and students, outdated course content, a biased assessment system, and lack of trained Human Resource. A major project to improve the quality of education at AIOU has been developed for the technological transformation of this unique national institution with the assistance of the Higher Education Commission of Pakistan. This paper discusses the technological and E-learning Model being implemented for the effective, responsive and target oriented Open and Distant Learning (ODL) at the University.
Discovery Learning and the Computational Experiment in Higher Mathematics and Science Education: A Combined Approach
Authors: Kyriazis Athanasios , Psycharis Sarantos , Korres Konstantinos
Published: December 2009

In this article we present our research for Discovery learning in relation to the computational experiment for the instruction of Mathematics and Science university courses, using the approach of the computational experiment through electronic worksheets. The approach is based on the principles of Discovery learning expanded with the principles of constructivist, socioâ??cultural and adult learning theories, the concept of computer based cognitive tools and the aspects on which the computational experiment is founded. Applications are presented using the software Mathematica and electronic worksheets for selected domains of Physics. We also present a case study, concerning the application of the computational experiment through electronic worksheets in the School of Pedagogical and Technological Education (ASPETE) during the spring semester of the academic year 2008â??2009. Research results concerning the impact of the above mentioned issues on studentsâ?? beliefs and learning performance are presented.
Combination of Bayesian Network and Overlay Model in User Modeling
Authors: Nguyen Loc , Do Phung
Published: December 2009

The core of adaptive system is user model containing personal information such as knowledge, learning styles, goalsâ?¦ which is requisite for learning personalized process. There are many modeling approaches, for example: stereotype, overlay, plan recognitionâ?¦ but they donâ??t bring out the solid method for reasoning from user model. This paper introduces the statistical method that combines Bayesian network and overlay modeling so that it is able to infer userâ??s knowledge from evidences collected during userâ??s learning process.
Integrating Adaptive Functionality in a LMS
Authors: Van der Sluijs Kees , Höver Kai Michael
Published: December 2009

Learning management systems are becoming more and more important in the learning process in both educational and corporate settings. They can nowadays even be used to server actual courses to the learner. However, one important feature is lacking in learning management systems: personalization. In this paper we look into this issue of personalization that enables courses to be adapted to the knowledge level and learning preferences of the user. We shortly review the state of the art in adaptive systems that allow creating adaptive courses. Then, exemplified in the popular LMS called CLIX we look at the authoring of an adaptive Business English course. We demonstrate how such a static course can be made adaptive by using the GALE adaptive engine. We then show that GALE can be integrated into CLIX, and in other LMSs as well, so that personalization and adaptation can become widely established technology.
Agent-Based Approach for E-Learning
Authors: Bourekkache Samir , Kazar Okba
Published: December 2009

The current life knows a remarkable development which changes all aspects of our life such as: our working environment, educational system, traveling patterns, sport activitiesâ?¦etc. The busy lifestyle faced by individuals today and the fast pattern of life may lead to their inability to be involved in a process of education. There is also a considerable technological development, especially the development of computing and communication technology. All these factors led to the idea of the need to reduce the time and to benefit from this technology, particularly in the field of education. The way of the classical education is very slow, and the student is obliged to be present at specific times which may be inappropriate for the majority of learners. Moreover, the substantial funds allocated for the success of classical learning process. Thus, it emerged the so-called E-learning via the Internet; the aims of this new mode of learning across the network (web) are to reduce the time of a process of learning â??education- as well as to erase the drawbacks of the classical way of education. Therefore, in E-learning, the learner is not forced to be present at specific times, but he is free to choose the time of learning, which is appropriate with his schedule. Another point that is the adaptation of the content (courses) with the intellectual and social characteristics of the learner and with his background (previous knowledge), which is the main task for each educational system. The technology of Multiagent system is relevant in this area.
Efficient Method for the Synthesis of Optically Active 2‐Amino‐2‐chromene Derivatives via One‐Pot Tandem Reactions
Authors: Xie Jian‐Wu , Huang Xiong , Fan Li‐Ping , Xu Dong‐Cheng , Li Xin‐Sheng , Su Hong , Wen Yi‐Hang
Published: December 2009

The asymmetric synthesis of functionalized 2‐amino‐2‐chromene derivatives with high enantioselectivities via one‐pot tandem reactions of functionalized α,β‐unsaturated ketones with malononitrile catalyzed by 9‐amino‐9‐deoxyepiquinine (1a) in combination with (R)‐1,1′‐binaphth‐2,2′‐diyl hydrogen phosphate (1c) is reported for the first time.
Preparation of Arylphosphonates by Palladium(0)‐Catalyzed Cross‐Coupling in the Presence of Acetate Additives: Synthetic and Mechanistic Studies
Authors: Kalek Marcin , Jezowska Martina , Stawinski Jacek
Published: December 2009

An efficient protocol for the synthesis of arylphosphonate diestersviaa palladium‐catalyzed cross‐coupling of H‐phosphonate diesters with aryl electrophiles, promoted by acetate ions, was developed. A significant shortening of the cross‐coupling time in the presence of the added acetate ions was achieved for bidentate and monodentate supporting ligands, and for different aryl electrophiles (iodo, bromo and triflate derivatives). The reaction conditions were optimized in terms of amount of the catalyst, supporting ligands, and source of the acetate ion used. Various arylphosphonates, including those of potential biological significance, were synthesized using this newly developed protocol. Some mechanistic aspects of the investigated reactions are also discussed.
Circadian variation in salivary testosterone across age classes in Ache Amerindian males of Paraguay
Authors: Bribiescas Richard G. , Hill Kim R.
Published: December 2009

Testosterone levels exhibit a circadian rhythm in healthy men, with morning levels tending to be higher compared to evening titers. However, circadian rhythms wane with age. Although this has been described in males living within industrialized settings, age‐related changes have not received similar attention in populations outside these contexts. Because many nonindustrialized populations, such as Ache Amerindians of Paraguay, exhibit testosterone levels that are lower than what is commonly reported in the clinical literature and lack age‐associated variation in testosterone, it was hypothesized that Ache men would not show age‐related variation in testosterone circadian rhythms. Diurnal rhythmicity in testosterone within and between Ache men in association with age (n = 52; age range, 18–64) was therefore examined. A significant negative association was evident between the ratio of morning and evening salivary testosterone and age (r = −0.28, P = 0.04). Men in their third decade of life exhibited significant diurnal variation (P = 0.0003), whereas older and younger age classes did not. Men between the ages of 30 and 39 also exhibited a higher AM:PM testosterone ratio compared to 40–49 and 50< year old men (P = 0.002, 0.006). Overall, declines in testosterone with aging may not be universal among human males, however, within‐individual analyses of diurnal variation capture age‐related contrasts in daily testosterone fluctuations. Circadian rhythmicity differs with age among the Ache and may be a common aspect of reproductive senescence among men regardless of ecological context. Am. J. Hum. Biol., 2010. © 2009 Wiley‐Liss, Inc.
“Lucy” redux: A review of research on Australopithecus afarensis
Authors: Kimbel William H. , Delezene Lucas K.
Published: December 2009

In the 1970s, mid‐Pliocene hominin fossils were found at the sites of Hadar in Ethiopia and Laetoli in Tanzania. These samples constituted the first substantial evidence for hominins older than 3.0 Ma and were notable for some remarkable discoveries, such as the “Lucy” partial skeleton and the abundant remains from the A.L. 333 locality at Hadar and the hominin footprint trail at Laetoli. The Hadar and Laetoli fossils were ultimately assigned to the novel hominin species Australopithecus afarensis, which at the time was the most plesiomorphic and geologically ancient hominin taxon. The discovery and naming of A. afarensis coincided with important developments in theory and methodology in paleoanthropology; in addition, important fossil and genetic discoveries were changing expectations about hominin divergence dates from extant African apes. This coincidence of events ensured that A. afarensis figured prominently in the last 30 years of paleoanthropological research. Here, the 30+ year history of discovery, analysis, and interpretation of A. afarensis and its contexts are summarized and synthesized. Research on A. afarensis continues and subject areas in which further investigation is needed to resolve ongoing debates regarding the paleobiology of this species are highlighted. Yrbk Phys Anthropol 52:2–48, 2009. © 2009 Wiley‐Liss, Inc.
The Anatomy and Physiology of the Venous Foot Pump
Authors: Corley Gavin J. , Broderick Barry J. , Nestor Sarah M. , Breen Paul P. , Grace Pierce A. , Quondamatteo Fabio , Ólaighin Gearóid
Published: December 2009

The presence of a venous pumping mechanism in the foot may be significant for venous return in the lower extremities. However, there has been a lack of conclusive research in the area to date and controversy still exists over the detailed anatomy and physiologic mechanism of the venous foot pump. A full understanding of the anatomy and physiology of the venous foot pump is essential for designing effective interventions for the prevention, treatment, and management of venous disease in the lower limbs. This article highlights and discusses the relevant literature relating to the anatomy and physiology of the venous foot pump. In addition, the plantar aspects of 10 cadaveric feet were dissected. These dissections revealed the presence of a previously unreported secondary deep plantar arch and/or deep system of venous connections in the foot and facilitated a more detailed description of the patterns of doubling and branching of the primary veins of the foot. The results of these dissections are discussed within the context of previous work in the field with the aid of detailed diagrams of the dissected feet and may provide a backdrop for the physiology of the venous foot pump and its potential role in lower limb circulation. This is discussed in the last section of the article, which also highlights existing controversy regarding the role of weight bearing and muscular contraction as the dominant mechanisms for venous pumping in the foot. Anat Rec, 2010. © 2009 Wiley‐Liss, Inc.
Synthesis of Imidazole Derivatives with Antimycobacterial Activity
Authors: Miranda Pedro O. , Gundersen Lise‐Lotte
Published: December 2009

4‐Substituted 1‐(p‐methoxybenzyl)imidazoles were designed and synthesized in order to mimic parts of the structure of highly potent antimycobacterial 6‐aryl‐9‐(p‐methoxybenzyl)purines. 4‐Haloimidazoles were subjected to Pd‐catalyzed cross‐coupling in order to introduce a (hetero)aryl group, or they were converted to Grignard reagents and reacted with (hetero)arylaldehydes. Further transformations of the adducts gave a variety of potential antimycobacterials with different “spacers” between the imidazole and (hetero)aryl group. The adduct from furfural was rearranged to a cyclopentenone derivative when treated with methanol under acidic conditions. Several target compounds exhibited antimycobacterial activity in vitro (IC90 13 μg/mL for the best inhibitors), but they were not as active as the most potent purines and pyrimidines synthesized before.
Predictive modeling of non‐viral gene transfer
Authors: Schwake Gerlinde , Youssef Simon , Kuhr Jan‐Timm , Gude Sebastian , David Maria Pamela , Mendoza Eduardo , Frey Erwin , Rädler Joachim O.
Published: December 2009

In non‐viral gene delivery, the variance of transgenic expression stems from the low number of plasmids successfully transferred. Here, we experimentally determine Lipofectamine‐ and PEI‐mediated exogenous gene expression distributions from single cell time‐lapse analysis. Broad Poisson‐like distributions of steady state expression are observed for both transfection agents, when used with synchronized cell lines. At the same time, co‐transfection analysis with YFP‐ and CFP‐coding plasmids shows that multiple plasmids are simultaneously expressed, suggesting that plasmids are delivered in correlated units (complexes). We present a mathematical model of transfection, where a stochastic, two‐step process is assumed, with the first being the low‐probability entry step of complexes into the nucleus, followed by the subsequent release and activation of a small number of plasmids from a delivered complex. This conceptually simple model consistently predicts the observed fraction of transfected cells, the cotransfection ratio and the expression level distribution. It yields the number of efficient plasmids per complex and elucidates the origin of the associated noise, consequently providing a platform for evaluating and improving non‐viral vectors. Biotechnol. Bioeng. 2010. 105: 805–813. © 2009 Wiley Periodicals, Inc.
Alteration of bacterial surface electrostatic potential and pH upon adhesion to a solid surface and impacts to cellular bioenergetics
Authors: Hong Yongsuk , Brown Derick G.
Published: December 2009

In our previous study [Hong Y, Brown DG (2009) Appl Environ Microbiol 75(8):2346–2353], the adenosine triphosphate (ATP) level of adhered bacteria was observed to be 2–5 times higher than that of planktonic bacteria. Consequently, the proton motive force (Δp) of adhered bacteria was approximately 15% greater than that of planktonic bacteria. It was hypothesized that the cell surface pH changes upon adhesion due to the charge‐regulated nature of the bacterial cell surface and that this change in surface pH can propagate to the cytoplasmic membrane and alter Δp. In the current study, we developed and applied a charge regulation model to bacterial adhesion and demonstrated that the charge nature of the adhering surface can have a significant effect on the cell surface pH and ultimately the affect the ATP levels of adhered bacteria. The results indicated that the negatively charged glass surface can result in a two‐unit drop in cell surface pH, whereas adhesion to a positively charged amine surface can result in a two‐unit rise in pH. The working hypothesis indicates that the negatively charged surface should enhance Δp and increase cellular ATP, while the positively charged surface should decrease Δp and decrease ATP, and these results of the hypothesis are directly supported by prior experimental results with both negatively and positively charged surfaces. Overall, these results suggest that the nature of charge on the solid surface can have an impact on the proton motive force and cellular ATP levels. Biotechnol. Bioeng. 2010;105: 965–972. © 2009 Wiley Periodicals, Inc.
Promoting adolescent sense of coherence: Testing models of risk, protection, and resiliency
Authors: Evans William Paul , Marsh Shawn C. , Weigel Daniel J.
Published: December 2009

Sense of coherence (SOC) is a dispositional trait that has been linked to well‐being in a broad range of populations and contexts. Little is known, however, about the factors associated with SOC development and maintenance across the lifespan. Conceptualized as a condition of resiliency, SOC in adolescents was explored via measures of risk and protection as reported on by 8th and 10th grade students (N = 1619). Employing cumulative indexes of protection and risk, analyses focused on testing four models of resiliency. Further, the relative and cumulative effects of protection and risk were explored across ecological domains. Analyses revealed support for the compensatory model of resiliency for males and females, while the challenge model also was supported for females. Analyses also revealed that protection and risk influencing SOC emerge at multiple domains for males and females. In addition, protective factors present at multiple domains were related to higher SOC while risk factors present at multiple domains were related to lower SOC regardless of gender. Results suggest a resiliency framework that considers multiple ecological domains is useful for understanding SOC in adolescents. Implications for additional research are presented. Copyright © 2008 John Wiley & Sons, Ltd.
Comorbidity, body mass index, and age and the risk of nonprostate‐cancer‐specific mortality after a postradiation prostate‐specific antigen recurrence
Authors: Nguyen Paul L. , Chen Ming‐Hui , Beard Clair J. , Suh W. Warren , Choueiri Toni K. , Efstathiou Jason A. , Hoffman Karen E. , Loffredo Marian , Kantoff Philip W. , D'Amico Anthony V.
Published: December 2009

BACKGROUND:

Some men with a postradiation therapy (RT) prostate‐specific antigen (PSA) recurrence will die of noncancer causes before developing metastases. Therefore, our ability to determine who would benefit from salvage hormonotherapy (HT) would be enhanced if an individual's risk of nonprostate‐cancer‐specific mortality were known.

METHODS:

Among 206 men with unfavorable‐risk localized prostate cancer initially randomized to RT+/−HT, 87 men who experienced PSA recurrence were studied. Fine and Gray's competing risks regression was used to assess whether body mass index (BMI) and the Adult Comorbidity Evaluation‐27 comorbidity level at randomization were associated with the risk of nonprostate‐cancer‐specific mortality after PSA recurrence, adjusting for age at recurrence.

RESULTS:

After a median postrecurrence follow‐up of 4.4 years, moderate/severe comorbidity (adjusted hazard ratio [HR] = 3.15; P = .02), BMI ≥ median (27.4 kg/m2; adjusted HR=2.98; p=.04), and increasing age at recurrence (adjusted HR = 1.17; P = .03) were significantly associated with an increased risk of nonprostate‐cancer‐specific mortality. Five‐year cumulative incidence estimates of nonprostate‐cancer‐specific mortality were as follows: 0% (95% confidence interval [CI] [0,0]) for low‐risk patients (mild/no comorbidity and age<median [76.2 years] and BMI<median), 18.8% (5.8‐31.8) for intermediate‐risk patients (mild/no comorbidity and either age≥median or BMI≥median); and 37.9% (95% CI, 6.8‐68.9) for high‐risk patients (moderate/severe comorbidity; P = .03 overall).

CONCLUSIONS:

After a post‐RT PSA recurrence, men with moderate/severe comorbidity and those who are obese or older face a substantial risk of nonprostate‐cancer‐specific mortality, and they could be considered for surveillance protocols with a plan to initiate salvage HT if the PSA rises rapidly (eg, PSA doubling time <6 months) or the patient develops clinically or radiographically evident disease. Cancer 2010. © 2009 American Cancer Society.
Use of the Diels–Alder Cycloaddition of Tetracyclone and Internal Aryl Acetylenes for the Synthesis of Functionalized Atrop­isomeric Biaryls
Authors: Hapke Marko , Gutnov Andrey , Weding Nico , Spannenberg Anke , Fischer Christine , Benkhäuser‐Schunk Christian , Heller Barbara
Published: December 2009

The Diels–Alder cycloaddition reaction of tetracyclone and functionalized, internal aryl acetylenes gave access to a number of bulky atropisomeric biaryls in good to excellent yield. The synthesis is convenient and yields the pure biaryls without tedious work‐up and purification procedures. Exemplarily the atropisomers have been resolved via the diastereomers in an easy and efficient manner to yield the enantiomers.
Ezetimibe reverses the inhibitory effects of dietary cholesterol on mammary tumorigenesis in rats
Authors: McNamara Erin , Archer Michael C.
Published: December 2009

There are concerns regarding increased cancer incidence in patients treated with ezetimibe, an inhibitor of the absorption of dietary cholesterol. Here we tested the hypothesis that ezetimibe will accelerate mammary tumorigenesis in rats. The drug was administered at a dose of 1 ppm in an AIN‐93G diet that contained 0.3% cholesterol. This experimental diet and control diets that contained either no additions or cholesterol or ezetimibe only, were fed to groups of 30 Sprague‐Dawley rats 3 days after they were treated with 50 mg/kg methylnitrosourea (MNU). All rats were euthanized 22 weeks after MNU administration. Tumor multiplicity was significantly smaller in rats fed cholesterol than those fed no cholesterol (1.84 ± 0.42 vs. 3.86 ± 0.86 respectively, P < 0.05), but was significantly greater in the cholesterol/ezetimibe group than the group fed only cholesterol (3.48 ± 0.59 vs. 1.84 ± 0.42 respectively, P < 0.04). The average weight of tumors/rat was also significantly larger in the cholesterol/ezetimibe group than those fed cholesterol alone (5.67 ± 1.15 vs. 2.56 ± 0.71 respectively, P < 0.04). As expected, ezetimibe prevented the cholesterol raising effect of the dietary cholesterol. These results show that ezetimibe reverses the inhibitory effect of dietary cholesterol on the development of rat mammary tumors.
Current trends in quantitative proteomics
Authors: Elliott Monica H. , Smith Derek S. , Parker Carol E. , Borchers Christoph
Published: December 2009

It was inevitable that as soon as mass spectrometrists were able to tell biologists which proteins were in their samples, the next question would be how much of these proteins were present. This has turned out to be a much more challenging question. In this review, we describe the multiple ways that mass spectrometry has attempted to address this issue, both for relative quantitation and for absolute quantitation of proteins. There is no single method that will work for every problem or for every sample. What we present here is a variety of techniques, with guidelines that we hope will assist the researcher in selecting the most appropriate technique for the particular biological problem that needs to be addressed. We need to emphasize that this is a very active area of proteomics research—new quantitative methods are continuously being introduced and some ‘pitfalls’ of older methods are just being discovered. However, even though there is no perfect technique—and a better technique may be developed tomorrow—valuable information on biomarkers and pathways can be obtained using these currently available methods Copyright © 2009 John Wiley & Sons, Ltd.
Towards an understanding of international city break travel
Authors: Dunne Gerard , Flanagan Sheila , Buckley Joan
Published: December 2009

This paper explores city break tourism and, in particular, the distinctive characteristics of this form of travel. The city break is examined and compared with other types of trips. The research follows a sequential mixed methods approach involving both a visitor survey and in‐depth interviews. The findings show the international city break trip to have a number of distinctive characteristics. These are summarised into five main areas (5 Ds) — duration, distance, date flexibility, discretionary nature and destination travel party. These distinguishing features provide a useful insight into one of the most important yet least examined travel segments in tourism research. Copyright © 2009 John Wiley & Sons, Ltd.
The prevalence of laryngeal pathology in a treatment‐seeking population with dysphonia
Authors: Van Houtte Evelyne , Van Lierde Kristiane , D'Haeseleer Evelien , Claeys Sofie
Published: December 2009

Objectives/Hypothesis.

This article describes the prevalence of laryngeal pathology in a treatment‐seeking population with dysphonia in the Flemish part of Belgium.

Study Design.

Retrospective investigation.

Methods.

During a period of 5 years (2004–2008), data were collected from 882 patients who consulted with dysphonia at the ear, nose, and throat department of the University Hospital in Ghent (Belgium). Laryngeal pathology was diagnosed using videostroboscopy. Ages ranged from 4 years to 90 years.

Results.

Functional voice disorders were most frequently diagnosed (30%), followed by vocal fold nodule (15%), and pharyngolaryngeal reflux (9%). The role of age, gender, and occupation was investigated. Pathologies were significantly more common in females than in males, representing 63.8% and 36.2% of the population, respectively. Professional voice users accounted for 41% of the workforce population, with teachers as main subgroup. In professional voice users, functional dysphonia occurred in 41%, vocal fold nodules in 15%, and pharyngolaryngeal reflux in 11%. Our data were compared with data from other countries.

Conclusions.

Functional voice disorders were overall the most common cause of voice disorders (except in childhood), followed by vocal fold nodules and pharyngolaryngeal reflux. Professional voice users accounted for almost one half of the active population, with functional voice disorders as the main cause of dysphonia. Laryngoscope, 2010
Functional modulation of satellite cells in long‐term denervated human laryngeal muscle
Authors: Donghui Chen , Shicai Chen , Wei Wang , Fei Liu , Jianjun Jing , Gang Chen , Hongliang Zheng
Published: December 2009

Objectives/Hypothesis:

To evaluate the effects of long‐term denervation on satellite cells (SCs) as myogenic stem cells in human posterior cricoarytenoid (PCA) muscle.

Study Design:

Histological investigation of SCs and quantitative assessment of myoD and myogenin, which are two key myogenic regulatory factors.

Methods:

According to the course of denervation, denervated PCA muscles of 58 patients who suffered from traumatic unilateral vocal cord paralysis were divided into four groups: group A (6–12 months, 15 cases), group B (13–24 months, 17 cases), group C (25–36 months, 14 cases), and group D (more than 36 months, 12 cases). Normal PCA muscles (12 cases) were used as a control group. Immunofluorescence labeling was used to visualize the SCs. Transcription and protein expression levels of myoD and myogenin were assessed using real‐time quantitative polymerase chain reaction and Western blots, respectively.

Results:

MyoD‐ and myogenin‐positive cells and embryonic myosin heavy chain‐positive myofibers were detected in group A and most of the samples of group B. Transcription levels of myoD and myogenin were highly upregulated in groups A and B, whereas groups C and D showed no significant difference as compared to control. Protein expression levels of myoD and myogenin peaked in group A, which was significantly different than group B. In contrast, no expression was observed in the other groups.

Conclusions:

Activated SCs contribute to regenerative myogenesis in denervated laryngeal muscles through compensatory mechanisms. Laryngeal muscles exhibit persistent regenerative potential from the viewpoint of muscle SCs after less than 2 years of denervation. Laryngoscope, 2010