bluuebunny/crossref_metadata_2025 huggingface dataset:
Has AIDS Changed the Ethics of Human Subjects Research?
Authors: Levine Carol
Published: July 2007

Jay Katz has been a pioneer in exploring the ethics of human subjects research. We are all the more grateful because he has given us a map of the landmarks along the path of what he has called his personal odyssey. That intellectual journey, from the horrors of Auschwitz to the callous disregard of human rights in the Tuskegee syphilis study, can serve as a guide to us today as we attempt to measure and direct the impact of AIDS on the ethics and regulation of research.

Professor Katz's account of his odyssey begins with the sources of his concern. At Yale Law School in 1966, with his colleague Richard Donnelly, he began teaching what was probably the first semester-long seminar on human experimentation. In preparation he read for the first time the trial transcripts of the Nuremberg proccedings against the Nazi physicians. I had lost most of my cousins, aunts, and uncles in the Holocaust, he writes. How many of them, I wondered, had been condemned to participation in these experiments?
Conflict between Doctor and Patient
Authors: Wolf Susan M.
Published: July 2007

“The belief that doctors can act on behalf of patients denies the existence of inevitable conflict.”

—Jay Katz
Effect of propranolol on sympathetically mediated leg vasoconstriction in humans
Authors: Pellinger Thomas K. , Halliwill John R.
Published: July 2007

Sympatho‐excitatory manoeuvres are used to study vascular responsiveness in humans, but it is unclear if circulating adrenaline attenuates peripheral vasoconstriction during these manoeuvres. We hypothesized that vasoconstrictor responses to three manoeuvres (neck pressure, unilateral thigh‐cuff release and isometric handgrip) would be greater after the administration of the β‐adrenergic blocker propranolol. Seven men and six women underwent these manoeuvres while beat‐by‐beat arterial pressure (finger photoplethysmography), femoral mean blood velocity (Doppler ultrasound) and femoral artery diameter (edge‐detection software) were measured. Femoral vascular conductance was calculated as flow/pressure. Propranolol had no effect on baseline femoral vascular conductance (P > 0.05). As a result of neck pressure, femoral vascular conductance was reduced 23.9 ± 3.5% before vs. 33.2 ± 3.2% after infusion of propranolol (P= 0.033). After thigh‐cuff release, femoral vascular conductance declined 50.2 ± 5.8% before vs. 57.4 ± 9.6% after propranolol infusion (P= 0.496). During handgrip, femoral vascular conductance was reduced 47.2 ± 9.6% before vs. 55.2 ± 9.2% after propranolol administration (P= 0.447). After handgrip, women had a greater rise in conductance than men (women: 153 ± 16.2%; men: 36.4 ± 10.6%; P < 0.001), which was blunted by 54.8% by propranolol (P < 0.001 vs. control), but unaffected by propranolol in men (P= 0.355 vs. control). The finding that β‐adrenergic receptor‐mediated vasodilatation minimally affects vascular responses to these sympatho‐excitatory manoeuvres reinforces their utility in the investigation of sympathetic vascular regulation in humans. Interestingly, post‐handgrip hyperaemia is greater in women than men and is, in part, β‐adrenergic receptor mediated.
The Analysis of Tensegrity Structures for the Design of a Morphing Wing
Authors: Moored Keith W. , Bart-Smith Hilary
Published: July 2007

Current attempts to build fast, efficient, and maneuverable underwater vehicles have looked to nature for inspiration. However, they have all been based on traditional propulsive techniques, i.e., rotary motors. In the current study a promising and potentially revolutionary approach is taken that overcomes the limitations of these traditional methods—morphing structure concepts with integrated actuation and sensing. Inspiration for this work comes from the manta ray (Manta birostris) and other batoid fish. These creatures are highly maneuverable but are also able to cruise at high speeds over long distances. In this paper, the structural foundation for the biomimetic morphing wing is a tensegrity structure. A preliminary procedure is presented for developing morphing tensegrity structures that include actuating elements. To do this, the virtual work method has been modified to allow for individual actuation of struts and cables. The actuation response of tensegrity beams and plates are studied and results are presented. Specifically, global deflections resulting from actuation of specific elements have been calculated with or without external loads. Finally, a shape optimization analysis of different tensegrity structures to the biological displacement field will be presented.
An Approach to Integrated Multi-Disciplinary Turbomachinery Design
Authors: Jarrett Jerome P. , Dawes William N. , Clarkson P. John
Published: July 2007

Aeroengines are designed using fractured processes. Complexity has driven the design of such machines to be subdivided by specialism, customer, and function. While this approach has worked well in the past, with component efficiencies, current material performance, and the possibilities presented by scaling existing designs for future needs becoming progressively exhausted, it is necessary to reverse this process of disintegration. Our research addresses this aim. The strategy we use has two symbiotic arms. The first is an open data architecture from which existing disparate design codes all derive their input and to which all send their output. The second is a dynamic design process management system known as “SignPosting.” Both the design codes and parameters are arranged into complementary multiple level hierarchies: fundamental to the successful implementation of our strategy is the robustness of the mechanisms we have developed to ensure consistency in this environment as the design develops over time. One of the key benefits of adopting a hierarchical structure is that it confers not only the ability to use mean-line, throughflow, and fully 3D computational fluid dynamics techniques in the same environment, but also to cross specialism boundaries and to insert mechanical, material, thermal, electrical, and structural codes, enabling exploration of the design space for multi-disciplinary nonlinear responses to design changes and their exploitation. We present results from trials of an early version of the system applied to the redesign of a generic civil aeroengine core compressor. SignPosting has allowed us to examine the hardness of design constraints across disciplines which has shown that it is far more profitable not to strive for even higher aerodynamic performance, but rather to improve the commercial performance by maintaining design and part-speed pressure ratio stability and efficiency while increasing rotor blade creep life by up to 70%.
On the Dynamics of Bodies With Continual Mass Variation
Authors: Cveticanin L. , Kovacic I.
Published: July 2007

In this paper the differential equations of the general motion of the rigid body with continual mass variation are considered. The impact force and the impact torque that occur due to addition or separation of the body with velocity and angular velocity which differs from the velocity of mass center and angular velocity of the existing body are introduced. The theoretical consideration is applied for solving a real technical problem when the band winds up on the drum. The plane motion of the drum on which the band winds up is considered. The influence of the velocity of the band on the angular velocity of the drum and the motion of the drum mass center is obtained.
Molecular Testing in the Diagnosis and Management of Chronic Hepatitis B
Authors: Valsamakis Alexandra
Published: July 2007

Hepatitis B virus (HBV) is an enveloped virus with a small (3.2-kb) partially double-stranded DNA genome that causes acute and chronic infections. The impact of these infections on public health worldwide is enormous, with an estimated prevalence of 2 billion acute infections and 360 million chronic infections globally. This review focuses on chronic hepatitis B and the molecular assays used in its diagnosis and management. Background information, including that about features of the hepatitis B virion, viral replication, and epidemiology of infection, that is important for understanding chronic hepatitis B and molecular diagnostic tests for HBV is provided. To facilitate an understanding of the utility of molecular testing for chronic hepatitis B, the four stages of chronic hepatitis B infection that are currently recognized, as well as an additional entity, occult hepatitis B, that can be diagnosed only by sensitive nucleic acid amplification methods, are reviewed in detail, including available therapeutic agents. The molecular diagnostic content focuses on tests for HBV DNA quantification, genotyping, and mutation detection (including precore/core promoter and antiviral resistance mutations). The discussion of these tests encompasses their current utility and performance characteristics, drawing from current clinical guidelines and other studies from the literature. In recognition of the continual evolution of this field, the final section describes emerging molecular markers with future diagnostic potential.
Locating a site on the maize B chromosome that controls preferential fertilization
Authors: Carlson Wayne R.
Published: July 2007

In maize, the B chromosome can undergo nondisjunction at the second pollen mitosis, producing sperm with two B chromosomes and sperm with zero B chromosomes. Preferential fertilization is the ability of the sperm carrying two B chromosomes to transmit more frequently to the embryo of a kernel than the sperm lacking the B chromosome. A translocation involving the B chromosome and chromosome 9, TB-9Sb, has been used to study preferential fertilization. The B-9 chromosome has the same properties of nondisjunction and preferential fertilization as the standard B chromosome. Deletion derivatives of B-9, which lack the centric heterochromatin and possibly some adjacent euchromatin, were tested for their ability to induce preferential fertilization. They were found to lack the capacity for preferential fertilization.
Evolution toward asymmetrical gaits in Neotropical spiny rats (Rodentia: Echimyidae): evidences favoring adaptation
Authors: Rocha P.L.B. , Renous S. , Abourachid A. , Höfling E.
Published: July 2007

The torch tail rat, Trinomys yonenagae Rocha, 1995 (family Echimyidae), is the morphologically most divergent of the spiny rats. In this study, we evaluate the hypothesis that gaits preferentially used by this species evolved as an adaptation to the desert-like dunes where they live. We filmed spontaneous locomotion of T. yonenagae, Trinomys albispinus minor Reis and Pessôa, 1995, and Proechimys cayennensis (Desmarest, 1817) with a high-speed camera. We detected, for each of the 323 cycles of the reference forelimb recorded, the kind of gait developed, the time lags between the touchdown of each pair of limbs, and the relative velocity. Trinomys yonenagae walked twice as fast as P. cayennensis and T. a. minor using mainly the asymmetrical transverse gallop, half-bounds, and bounds, while the other two species used mainly the lateral sequence walk. Gaits changed from symmetrical to asymmetrical with increasing velocity for T. yonenagae but not for the other species. We argue that the gait pattern found in T. yonenagae is autapomorphic, that its origin coincides with the shift to a desert-like habitat, and that this type of gait confers higher adaptive value to explore resources in open areas than the plesiomorphic pattern. Therefore, we conclude that it can be considered adaptive to life in the dunes.
Role of TLR2, TLR4, and MyD88 in murine ozone-induced airway hyperresponsiveness and neutrophilia
Authors: Williams Alison S. , Leung Sum-Yee , Nath Puneeta , Khorasani Nadia M. , Bhavsar Pankaj , Issa Razao , Mitchell Jane A. , Adcock Ian M. , Chung Kian Fan
Published: July 2007

Exposure to air pollutants such as ozone (O3) induces airway hyperresponsiveness (AHR) and airway inflammation. Toll-like receptors (TLR) are first-line effector molecules in innate immunity to infections and signal via adapter proteins, including myeloid differentiation factor-88 (MyD88). We investigated the sensing of ozone by TLR2, TLR4, and MyD88. Ozone induced AHR in wild-type (WT) C57BL/6 mice, but AHR was absent in TLR2−/−, TLR4−/−, and MyD88−/− mice. Bronchoalveolar lavage neutrophilia induced by ozone was inhibited at 3 h but not at 24 h in TLR2−/− and TLR4−/− mice, while in MyD88−/− mice, this was inhibited at 24 h. We investigated the expression of inflammatory cytokines and TLR2, TLR4, and MyD88 in these mice. Ozone induced time-dependent increases in inflammatory gene expression of keratinocyte chemoattractant (KC) and IL-6 and of TLR2, TLR4, and MyD88 in WT mice. IL-6 and KC expression induced by ozone was inhibited in TLR2−/−, TLR4−/−, and MyD88−/− mice. Expression of MyD88 was increased in TLR2−/− and TLR4−/− mice, while induction of TLR2 or TLR4 was reduced in TLR2−/− and TLR4−/− mice, respectively. TLR2 and TLR4 mediate AHR induced by oxidative stress such as ozone, while the adapter protein MyD88, but not TLR2 or TLR4, is important in mediating ozone-induced neutrophilia. TLR2 and TLR4 may also be important in regulating the speed of neutrophilic response. Therefore, ozone may induce murine AHR and neutrophilic inflammation through the activation of the Toll-like receptor pathway that may sense noninfectious stimuli such as oxidative stress.
Short-term increases in intraluminal pressure reverse age-related decrements in endothelium-dependent dilation in soleus muscle feed arteries
Authors: Woodman Christopher R. , Trott Daniel W. , Laughlin M. Harold
Published: July 2007

We tested the hypothesis that short-term increases in intraluminal pressure improve endothelium-dependent dilation and increase endothelial nitric oxide (NO) synthase (eNOS) expression in senescent soleus muscle feed arteries (SFA). SFA isolated from young (4 mo) and old (24 mo) Fischer 344 rats were cannulated and pressurized at 90 (p90) or 130 (p130) cmH2O for 4 h. At the end of the 4-h protocol, pressure in p130 SFA was lowered to 90 cmH2O for examination of endothelium-dependent (flow- or ACh-induced) vasodilation. Flow- and ACh-induced dilations were blunted in old p90 SFA relative to young p90 SFA. Pretreatment with increased pressure (p130) improved flow- and ACh-induced dilations in old SFA, such that vasodilator responses were similar to those in young SFA. In the presence of Nω-nitro-l-arginine (l-NNA) or l-NNA + indomethacin (Indo), flow-induced dilation was inhibited in old p130 SFA, such that the response was not greater than the response in old p90 SFA. In old p130 SFA, ACh-induced dilation was inhibited by l-NNA + Indo (not l-NNA alone). In a separate experiment, SFA were pressurized at 70, 90, 110, or 130 cmH2O for 4 h, and eNOS mRNA and protein content were assessed. Increased pressure induced eNOS mRNA expression in young (not old) SFA. eNOS protein content was not altered in young or old SFA. These results indicate that short-term increases in intraluminal pressure improve endothelium-dependent dilation in senescent SFA, in part by enhancing NO bioavailability; however, the beneficial effect was not associated with increased eNOS expression.
Apparent diffusion time of oxygen from blood to tissue in rat cerebral cortex: implication for tissue oxygen dynamics during brain functions
Authors: Masamoto Kazuto , Kershaw Jeff , Ureshi Masakatsu , Takizawa Naosada , Kobayashi Hirosuke , Tanishita Kazuo , Kanno Iwao
Published: July 2007

To investigate the dynamics of tissue oxygen demand and supply during brain functions, we simultaneously recorded Po2 and local cerebral blood flow (LCBF) with an oxygen microelectrode and laser Doppler flowmetry, respectively, in rat somatosensory cortex. Electrical hindlimb stimuli were applied for 1, 2, and 5 s to vary the duration of evoked cerebral metabolic rate of oxygen (CMRO2). The electrical stimulation induced a robust increase in Po2 (4–9 Torr at peak) after an increase in LCBF (14–26% at peak). A consistent lag of ∼1.2 s (0.6–2.3 s for individual animals) in the Po2 relative to LCBF was found, irrespective of stimulus length. It is argued that the lag in Po2 was predominantly caused by the time required for oxygen to diffuse through tissue. During brain functions, the supply of fresh oxygen further lagged because of the latency of LCBF onset (∼0.4 s). The results indicate that the tissue oxygen supports excess demand until the arrival of fresh oxygen. However, a large drop in Po2 was not observed, indicating that the evoked neural activity demands little extra oxygen or that the time course of excess demand is as slow as the increase in supply. Thus the dynamics of Po2 during brain functions predominantly depend on the time course of LCBF. Possible factors influencing the lag between demand and supply are discussed, including vascular spacing, reactivity of the vessels, and diffusivity of oxygen.
Effects of High Fruit-Vegetable and/or Low-Fat Intervention on Breast Nipple Aspirate Fluid Micronutrient Levels
Authors: Djuric Zora , Chen Gang , Ren Jianwei , Venkatramanamoorthy Raghu , Covington Chandice Y. , Kucuk Omer , Heilbrun Lance K.
Published: July 2007

Background: A change in diet is known to affect micronutrient levels in blood but to what extent diet can affect micronutrient levels in the breast is not yet well established.

Methods: Healthy, premenopausal women with a family history of breast cancer were randomized across four diet arms for 1 year in a 2 × 2 factorial design study: control, low-fat, high fruit-vegetable, and combination low-fat/high fruit-vegetable diets. Subjects were asked to collect breast nipple aspirate fluid (NAF) at 0, 6, and 12 months, and levels of micronutrients were measured in the fluid.

Results: A total of 122 women were enrolled, 97 were retained for 12 months, and sufficient NAF for analysis was available from 59 women at baseline, 49 at 6 months, and 50 at 12 months. Repeated measures mixed-model ANOVA was used to model the data using cholesterol levels and lactation duration as covariates, where appropriate. The high fruit-vegetable intervention, regardless of fat intake, significantly increased total carotenoid levels in NAF. In the low-fat arm, levels of total carotenoids decreased over time relative to control. Levels of total tocopherols and retinol did not change significantly. Levels of 15-F2t-isoprostane, a marker of lipid peroxidation, also did not change significantly over time, although there was a decrease observed in the combination arm.

Conclusions: These results indicate that total carotenoid levels in NAF can be significantly increased in the breast NAF with a high fruit-vegetable diet. A low-fat diet that was achieved with little increase in fruit and vegetable intake, however, decreased NAF carotenoid levels. (Cancer Epidemiol Biomarkers Prev 2007;16(7):1393–9)
Mechanism of High Glucose–Induced Angiotensin II Production in Rat Vascular Smooth Muscle Cells
Authors: Lavrentyev Eduard N. , Estes Anne M. , Malik Kafait U.
Published: July 2007

Angiotensin II (Ang II), a circulating hormone that can be synthesized locally in the vasculature, has been implicated in diabetes-associated vascular complications. This study was conducted to determine whether high glucose (HG) (≈23.1 mmol/L), a diabetic-like condition, stimulates Ang II generation and the underlying mechanism of its production in rat vascular smooth muscle cells. The contribution of various enzymes involved in Ang II generation was investigated by silencing their expression with small interfering RNA in cells exposed to normal glucose (≈4.1 mmol/L) and HG. Angiotensin I (Ang I) was generated from angiotensinogen by cathepsin D in the presence of normal glucose or HG. Although HG did not affect the rate of angiotensinogen conversion, it decreased expression of angiotensin-converting enzyme (ACE), downregulated ACE-dependent Ang II generation, and upregulated rat vascular chymase–dependent Ang II generation. The ACE inhibitor captopril reduced Ang II levels in the media by 90% in the presence of normal glucose and 19% in HG, whereas rat vascular chymase silencing reduced Ang II production in cells exposed to HG but not normal glucose. The glucose transporter inhibitor cytochalasin B, the aldose reductase inhibitor alrestatin, and the advanced glycation end product formation inhibitor aminoguanidine attenuated HG-induced Ang II generation. HG caused a transient increase in extracellular signal-regulated kinase (ERK)1/2 phosphorylation, and ERK1/2 inhibitors reduced Ang II accumulation by HG. These data suggest that polyol pathway metabolites and AGE can stimulate rat vascular chymase activity via ERK1/2 activation and increase Ang II production. In addition, decreased Ang II degradation, which, in part, could be attributable to a decrease in angiotensin-converting enzyme 2 expression observed in HG, contributes to increased accumulation of Ang II in vascular smooth muscle cells by HG.
Anatomy of a Modal Construction
Authors: Fintel Kai von , Iatridou Sabine
Published: July 2007

Languages can express the existence of an easy way of achieving a goal in a construction we call the sufficiency modal construction (SMC), which combines a minimizing/exclusive operator like only or ne … que and a goal-oriented necessity modal like have to or need to, asin To get good cheese, you only have to go to the North End. We show that the morphosyntactic makeup of the SMC is crosslinguistically stable. We show that the semantics of the construction poses a severe compositionality problem. We solve the problem by giving the negation and the exclusive operator differential scope. For only, this means decomposing it into negation and an exclusive other than component.
The 10 sea urchin receptor for egg jelly proteins (SpREJ) are members of the polycystic kidney disease-1 (PKD1) family
Authors: Gunaratne H Jayantha , Moy Gary W , Kinukawa Masashi , Miyata Shinji , Mah Silvia A , Vacquier Victor D
Published: July 2007

Background

Mutations in the human polycystic kidney disease-1 (hPKD1) gene result in ~85% of cases of autosomal dominant polycystic kidney disease, the most frequent human monogenic disease. PKD1 proteins are large multidomain proteins involved in a variety of signal transduction mechanisms. Obtaining more information about members of the PKD1 family will help to clarify their functions. Humans have five hPKD1 proteins, whereas sea urchins have 10. The PKD1 proteins of the sea urchin, Strongylocentrotus purpuratus, are referred to as the Receptor for Egg Jelly, or SpREJ proteins. The SpREJ proteins form a subfamily within the PKD1 family. They frequently contain C-type lectin domains, PKD repeats, a REJ domain, a GPS domain, a PLAT/LH2 domain, 1–11 transmembrane segments and a C-terminal coiled-coil domain.

Results

The 10 full-length SpREJ cDNA sequences were determined. The secondary structures of their deduced proteins were predicted and compared to the five human hPKD1 proteins. The genomic structures of the 10 SpREJs show low similarity to each other. All 10 SpREJs are transcribed in either embryos or adult tissues. SpREJs show distinct patterns of expression during embryogenesis. Adult tissues show tissue-specific patterns of SpREJ expression.

Conclusion

Possession of a REJ domain of about 600 residues defines this family. Except for SpREJ1 and 3, that are thought to be associated with the sperm acrosome reaction, the functions of the other SpREJ proteins remain unknown. The sea urchin genome is one-fourth the size of the human genome, but sea urchins have 10 SpREJ proteins, whereas humans have five. Determination of the tissue specific function of each of these proteins will be of interest to those studying echinoderm development. Sea urchins are basal deuterostomes, the line of evolution leading to the vertebrates. The study of individual PKD1 proteins will increase our knowledge of the importance of this gene family.
Lower back pain in physically demanding college academic programs: a questionnaire based study
Authors: Brennan Graham , Shafat Amir , Donncha Ciarán Mac , Vekins Carmel
Published: July 2007

Background

Lower back pain (LBP) is ranked first as a cause of disability and inability to work, and is expected to affect up to 90% of the worlds population at some point in their lifetime. The annual first time incidence of LBP is 5%, and the annual prevalence (i.e. those suffering at time of questioning) is between 15 and 63%. Prospective studies demonstrate that low back problems do not display a six-week spontaneous recovery pattern, as was once believed. The condition is regularly seen to worsen over time, becoming a chronic disorder, influenced by both physical and psychosocial factors.

Methods

The current study assessed the level of LBP amongst students engaged in educational programs that were physically demanding, and its influence on lower back problems. A 1-year retrospective questionnaire consisting of 37 closed, open and multi-choice questions was designed to ascertain self-reported information on the occurrence, cause and type of LBP. Treatment, care seeking and general knowledge regarding LBP were also recorded. Students were enrolled in BSc Equine Science, BSc Physical Education and BSc Sports & Exercise Science degree programs and a total number of 188 valid questionnaires were collected.

Results

The self reported, anthropometrical data for participants in this study are: age 20.9 ± 2.7 yrs; height 171.8 ± 9.3 cm; weight 66.7 ± 10.4 kg; female 64% (n = 120), male 36% (n = 68). The overall self reported prevalence of LBP was 32% (n = 61). Within the LBP population, 77% reported their problem as recurring. Two factors showed significance as having an influence on LBP. They were age (21.6 ± 3.5 yrs, p = 0.005) and hours of personal training physical activity (14.0 ± 8.2 hrs per week, p = 0.02). LBP sufferers also displayed poor management of their condition and an interest in education and treatment of their problem.

Conclusion

The current study revealed high prevalence of LBP consistent with that of the literature, and unveiled a recurrence rate and behavioral habits of sufferers, which are warning signs of a more chronic state to come. Novel data presented here offers strong support for the need for prospective injury tracking, plus educational intervention and treatment aimed at prevention of LBP.
Haplotype of gene Nedd4 binding protein 2 associated with sporadic nasopharyngeal carcinoma in the Southern Chinese population
Authors: Zheng Mei-Zhen , Qin Hai-De , Yu Xing-Juan , Zhang Ru-Hua , Chen Li-Zhen , Feng Qi-Sheng , Zeng Yi-Xin
Published: July 2007

Background

Bcl-3 as an oncoprotein is overexpressed in nasopharyngeal carcinoma (NPC). Nedd4 binding protein 2 (N4BP2), which is located in the NPC susceptibility locus, is a Bcl-3 binding protein. This study is aimed to explore the association between N4BP2 genetic polymorphism and the risk of NPC.

Methods

We performed a hospital-based case-control study, including 531 sporadic NPC and 480 cancer-free control subjects from southern China. PCR-sequencing was carried out on Exons, promoter region and nearby introns of the N4BP2 gene. The expression pattern of N4BP2 and Bcl-3 was also analyzed.

Results

We observed a statistically significant difference in haplotype blocks ATTA and GTTG between cases and controls. In addition, three novel SNPs were identified, two of which were in exons (loc123-e3l-snp2, position 39868005, A/G, Met171Val; RS17511668-SNP2, position 39926432, G/A, Glu118Lys), and one was in the intron6 (RS794001-SNP1, position 39944127, T/G). Moreover, N4BP2 was at higher levels in a majority of tumor tissues examined, relative to paired normal tissues.

Conclusion

These data suggest that haplotype blocks ATTA and GTTG of N4BP2 is correlation with the risk of sporadic nasopharyngeal carcinoma in the Southern Chinese population and N4BP2 has a potential role in the development of NPC.
Housekeeping genes tend to show reduced upstream sequence conservation
Authors: Farré Domènec , Bellora Nicolás , Mularoni Loris , Messeguer Xavier , Albà M Mar
Published: July 2007

Background

Understanding the constraints that operate in mammalian gene promoter sequences is of key importance to understand the evolution of gene regulatory networks. The level of promoter conservation varies greatly across orthologous genes, denoting differences in the strength of the evolutionary constraints. Here we test the hypothesis that the number of tissues in which a gene is expressed is related in a significant manner to the extent of promoter sequence conservation.

Results

We show that mammalian housekeeping genes, expressed in all or nearly all tissues, show significantly lower promoter sequence conservation, especially upstream of position -500 with respect to the transcription start site, than genes expressed in a subset of tissues. In addition, we evaluate the effect of gene function, CpG island content and protein evolutionary rate on promoter sequence conservation. Finally, we identify a subset of transcription factors that bind to motifs that are specifically over-represented in housekeeping gene promoters.

Conclusion

This is the first report that shows that the promoters of housekeeping genes show reduced sequence conservation with respect to genes expressed in a more tissue-restricted manner. This is likely to be related to simpler gene expression, requiring a smaller number of functional cis-regulatory motifs.
The Application of Lean Thinking to the Care of Patients With Bone and Brain Metastasis With Radiation Therapy
Authors: Kim Christopher S. , Hayman James A. , Billi John E. , Lash Kathy , Lawrence Theodore S.
Published: July 2007

Purpose

Patients with bone and brain metastases are among the most symptomatic nonemergency patients treated by radiation oncologists. Treatment should begin as soon as possible after the request is generated. We tested the hypothesis that the operational improvement method based on lean thinking could help streamline the treatment of our patients referred for bone and brain metastases.

Methods

University of Michigan Health System has adopted lean thinking as a consistent approach to quality and process improvement. We applied the principles and tools of lean thinking, especially value as defined by the customer, value stream mapping processes, and one piece flow, to improve the process of delivering care to patients referred for bone or brain metastases.

Results and Conclusion

The initial evaluation of the process revealed that it was rather chaotic and highly variable. Implementation of the lean thinking principles permitted us to improve the process by cutting the number of individual steps to begin treatment from 27 to 16 and minimize variability by applying standardization. After an initial learning period, the percentage of new patients with brain or bone metastases receiving consultation, simulation, and treatment within the same day rose from 43% to nearly 95%. By implementing the ideas of lean thinking, we improved the delivery of clinical care for our patients with bone or brain metastases. We believe these principles can be applied to much of the care administered throughout our and other health care delivery areas.
Liver X Receptor-α Gene Expression Is Positively Regulated by Thyroid Hormone
Authors: Hashimoto Koshi , Matsumoto Shunichi , Yamada Masanobu , Satoh Teturou , Mori Masatomo
Published: July 2007

The nuclear oxysterol receptors, liver X receptors (LXRs), and thyroid hormone receptors (TRs) cross talk mutually in many aspects of transcription, sharing the same DNA binding site (direct repeat-4) with identical geometry and polarity. In the current study, we demonstrated that thyroid hormone (T3) up-regulated mouse LXR-α, but not LXR-β, mRNA expression in the liver and that cholesterol administration did not affect the LXR-α mRNA levels. Recently, several groups have reported that human LXR-α autoregulates its own gene promoter through binding to the LXR response element. Therefore, we examined whether TRs regulate the mouse LXR-α gene promoter activity. Luciferase assays showed that TR-β1 positively regulated the mouse LXR-α gene transcription. Analysis of serial deletion mutants of the promoter demonstrated that the positive regulation by TR-β1 was not observed in the −1240/+30-bp construct. EMSA(s) demonstrated that TR-β1 or retinoid X receptor-α did not bind to the region from −1300 to −1240 bp (site A), whereas chromatin-immunoprecipitation assays revealed that TR-β1 and retinoid X receptor-α were recruited to the site A, indicating the presence of intermediating protein between the nuclear receptors and DNA site. We also showed that human LXR-α gene expression and promoter activities were up-regulated by thyroid hormone. These data suggest that LXR-α mRNA expression is positively regulated by TR-β1 and thyroid hormone at the transcriptional level in mammals. This novel insight that thyroid hormone regulates LXR-α mRNA levels and promoter activity should shed light on a cross talk between LXR-α and TR-β1 as a new therapeutic target against dyslipidemia and atherosclerosis.
Functional interactions between Prp8, Prp18, Slu7, and U5 snRNA during the second step of pre-mRNA splicing
Authors: Aronova Anna , Bacíková Dagmar , Crotti Luciana B. , Horowitz David S. , Schwer Beate
Published: July 2007

After the second transesterification step of pre-mRNA splicing, the Prp22 helicase catalyzes release of spliced mRNA by disrupting contacts in the spliceosome that likely involve Prp8. Mutations at Arg1753 in Prp8, which suppress helicase-defective prp22 mutants, elicit temperature-sensitive growth phenotypes, indicating that interactions in the spliceosome involving Prp8-R1753 might be broken prematurely at 37°C. Here we report that mutations in loop I of the U5 snRNA or in Prp18 can suppress the temperature-sensitive prp8-R1753 mutants. The same gain-of-function PRP18 alleles can also alleviate the growth phenotypes of multiple slu7-ts mutants, indicating a functional link between Prp8 and the second step splicing factors Prp18 and Slu7. These findings, together with the demonstration that changes at Arg1753 in Prp8 impair step 2 of pre-mRNA splicing in vitro, are consistent with a model in which (1) Arg1753 plays a role in stabilizing U5/exon interactions prior to exon joining and (2) these contacts persist until they are broken by the helicase Prp22.
Surface tension lowering substance in eustachian tube function
Authors: Hagan Warren E.
Published: July 2007

Direct evidence is presented that establishes the existence of an Eusta‐chian tube surface tension lowering substance (S.T.L.S.) in the canine experimental model. The physiological role of this Eustachian tube S.T.L.S. is to facilitate middle ear ventilation by lowering the opening pressure needed to aerate the Eustachian tube and middle ear. While S.T.L.S. possesses characteristics similar to those of the pulmonary surfactant, experimental data suggest that it does not reduce the surface tension in the auditory conduit of the middle ear to the degree that the surfactant does in pulmonary system. Neither does Eustachian S.T.L.S. exhibit the physical characteristic of “hysteresis” that the alveolar surfactant demonstrates.

The paper presents brief discussion of the physical phenomenon of surface tension as it exists in the Eustachian tube. Various methods of physical surface chemistry used in measuring the surface pressure of the canine Eustachian S.T.L.S. extract are discussed, including criticism of the indirect methodology of previous researchers in investigating the possibility of an Eustachian tube S.T.L.S. Direct methodology, utilizing the Langmuir Trough with Wilhelmy surface balance, was employed.

S.T.L.S. is considered in its physiologic role in maintaining Eustachian tube patency. It is suggested that a decreased amount of Eustachian S.T.L.S. may be implicated in the pathophysiology of the serous acellular sterile middle ear transudate in serous otitis media. Finally, it is stressed that this preliminary work needs further histochemical and physiological investigation.
Nystagmus responses to water and air caloric stimulation in clinical populations
Authors: Suter Charles M. , Blanchard Cyrus L. , Cook‐Manokey Brenda E.
Published: July 2007

The nystagmus responses of two groups of patients referred for electronystagmography were compared to test for differences between air and water caloric stimulation. Responses from patients with spontaneous or positional nystagmus or who showed greater than 30% directional preponderance or excitability of labyrinth were removed from the data. The 30% C and 44% C water and the 24% C air produced equivalent responses. The 50% C air produced responses with slow component velocities greater than expected; however, the distributions of computed directional preponderance and excitability of labyrinth showed no differences between the air and water caloric stimulation.
Criteria for selection of patients undergoing paranasal sinus surgery
Authors: Eichel Berkley S.
Published: July 2007

A three year study was begun in January 1971, during which time all patients with paranasal sinus problems were carefully studied in an effort to determine which patients were surgical candidates. A total of 756 patients were seen; 154 had sufficient disease to qualify for this study. A basic medical regimen was prescribed for all of these patients unless their problem seemed too emergent to delay surgery. This regimen utilized antibiotics and antihistamine‐decongestants followed by interval radiographic examinations. A total of 48 of the 154 patients eventually required a surgical procedure.

Sixteen patients required immediate surgery and did not have interval radiographic examinations. The prime reason for immediate surgery was the suspicion of neoplasm or impending complications such as osteomyelitis of the frontal bone, the so‐called “complicated acute sinusitis.” Thirty‐two patients underwent a surgical procedure after a trial period of conservative medical management failed to significantly improve their status. The majority of these patients had obstructive nasal polyposis and sinusitis. Another major indication for sinus surgery was the persistence of a unilateral opaque antrum.

Sixty‐eight patients treated conservatively improved sufficiently either clinically or radiographically to eliminate the need for initial surgical intervention. One of these patients later required surgery. Thirty‐eight patients did not come back for re‐examination and re‐X‐ray and were classified as lost to follow‐up.

The majority of patients undergoing the pansinus operative procedure which includes a bilateral nasal polypectomy, bilateral intranasal eth‐moidectomy and bilateral nasal antral windows, were noted to have good to excellent results when seen and studied a minimum of one year following surgery. A lesser percentage of favorable results occurred in those patients undergoing a Caldwell‐Luc procedure, especially on a delayed basis. The need to study those cases requiring Caldwell‐Luc exploration, because of persistent radiographic opacification or sinus polyps with associated symptoms, is discussed. A trial period of medical management in the 154 cases ended up with only eight Caldwell‐Luc and two intranasal ethmoidectomy patients who did not gain therapeutic or diagnostic benefit from their operative procedures. The utilization of unidirectional or poly‐directional tomography will hopefully resolve this problem and eliminate the moderately high percentage of negative explorations.

Many of the diagnostic terms used preoperatively were found to be inaccurate via surgical exploration. It is the contention of this study that more descriptive terms such as: bilateral obstructive nasal polyposis, antral choanal polyp, and a radiographic opacified maxillary sinus are more objective and meaningful, and would probably aid in the overall standardization and understanding of what constitutes the need for para‐nasal sinus surgery.
Clinical assessment of eustachian tube ventilatory function
Authors: Cohn Arnold M.
Published: July 2007

The persisting incidence of middle ear effusion subsequent to the advent of antibiotics and the development of a sophisticated microsurgical armamentarium and technique has been the continuing impetus to arrive at a method for evaluating eustachian tube function. The aspiration test developed by Flisberg, et al., has been thought to test most satisfactorily physiological tubal function by measuring the capability of the tube to equilibrate an induced negative pressure in the middle ear by deglutition.

This technique was utilized to evaluate tubal function in 92 ears with tympanic membrane perforations. In 21 ears perforation was the result of trauma, recent but not acute. The remaining 71 ears have persistent perforations as a result of chronic otitis media; 18 ears were actively draining when they were tested; 53 ears were dry, without evidence of drainage, at the time of test.

This investigation has shown that ears presenting dry perforations as a result of chronic otitis media demonstrate a continuum of function from full capability to reduce negative pressure to total inability to reduce such pressures; that no discernable difference in eustachian tube performance exists, however, among ears with quiescent perforations as a result of trauma or chronic otitis media; that active drainage manifesting an inflammatory mucosal process further severely compromises tubal ventila‐tory function by facilitating “locking” at high negative pressures; that age, while exerting some influence on the tube, in that adults show some increased capability for tubal function and some compromise in such function is present in childhood, that the influence of age is hardly striking; that tubes manifesting a total inability to reduce negative pressure do tend to be associated with ears with recurrent or refractory mucosal disease.

However, this technique may also be challenged. It has been suggested that normal tubes should be capable of reducing negative pressure to within zero to ‐50 mm H2O. Other studies, however, have shown little correlation between middle ear pressure as measured by tympanometry and tubal function tested by this method. A disparity also exists in the high incidence of poor tubal function by this technique as compared to the success rates in tympanoplasty in existing large series; that while some investigators are able to demonstrate the tendency for poorer results in ears with poor tubal function testing, prediction of surgical success and failure is feasible in only a minority.

It is the conclusion of this study that a negative result in testing for eustachian tube function is not a contraindication to tympanoplasty, and it is difficult to enthusiastically support this test as being capable of measuring the physiological normal of the tube or as a prognostic indicator to results in tympanoplasty.
Chronic otitis media and hearing loss in the eskimo population of canada
Authors: Baxter James D.
Published: July 2007

Chronic otitis media and hearing loss is a major health problem today in the Canadian Eskimo. The subject is reviewed and the findings of projects and a survey that have been carried out recently are discussed. A modality of treatment is proposed which is based upon the findings of the projects, the survey and other information that is available at the present time.
‘Surrendering’ the Fugitive—The European Arrest Warrant and the United Kingdom
Authors: Mackarel Mark
Published: July 2007

This article explains how the European Arrest Warrant forms part of the response to the modern needs of the European Union in dealing with transnational crime and considers the experience of the UK in implementing and using the warrant. The warrant is the first manifestation of the EU policy of mutual recognition in relation to cooperation in criminal matters and in questioning how effectively the UK has put the warrant into operation under the Extradition Act 2003, the article compares the analyses of the European Commission, Eurojust and the House of Lords. Finally, the approach to interpretation taken by the courts to cases coming before them concerning the warrant under the 2003 Act is examined.
Morphometrics and ecology of Myotis cf. punicus (Chiroptera, Vespertilionidae) in Corsica
Authors: Beuneux Grégory
Published: July 2007

The presence of the Maghrebian bat, Myotis cf. punicus Felten, 1977, is
reported from Corsica where it is found in low numbers throughout the
island, at altitudes between 0 and 1480 m. Most of winter roosts and all
breeding colonies are recorded at the lowest altitudes in bridges, caves, mines
and buildings. Maghrebian bats forage in open habitats and prey up on
Orthoptera, Coleoptera and Lepidoptera (caterpillars). The conservation
status is discussed.
The importance of small cellars to bat hibernation in Poland
Authors: Lesiński Grzegorz , Kowalski Marek , Domański Jarosław , Dzięciołowski Radosław , Laskowska-Dzięciołowska Krystyna , Dzięgielewska Magdalena
Published: July 2007

Inspections of 521 small cellars inhabited by bats in Poland revealed the
occurrence of 10 species: Myotis myotis, M. nattereri, M, brandtii, M. dasycneme,
M. daubentonii, Eptesicus nilssonii, E. serotinus, Plecotus auritus, P. austriacus,
and Barbastella barbastellus. P. auritus was the most frequent and
abundant (410 sites, 54.5% records). M. daubentonii dominated in cellars of
the NW and NE regions of the country, while P. austriacus was the most
abundant in the SW region. Communities of bats hibernating in small cellars and large underground hibernacula differed significantly. Plecotus spp. clearly
preferred small hibernation sites, while M. myotis large ones. Species richness
and diversity were highest in NW and NE region where this type of roost had
greatest importance to bat hibernation. Despite the fact that only single individuals
occurred in 44.7% of cellars, these roosts, common and numerous in
Poland, could be in total inhabited by tens of thousands of bats yearly.
Elements of Cognitive Robotics (Elemente kognitiver Robotik)
Authors: Goerick Christian , Körner Edgar
Published: July 2007

In this paper we present our research aiming at creating a cognitive humanoid. We describe our understanding of the core elements of a processing architecture for such kind of an artifact. After these conceptual considerations we present our research results in the areas of task and body oriented motion control as well as visually and behaviorally oriented learning.
LOLA – a Performance Enhanced Humanoid Robot (LOLA – ein leistungsgesteigerter humanoider Roboter)
Authors: Buschmann Thomas , Lohmeier Sebastian , Kühnlenz Kolja , Buss Martin , Ulbrich Heinz , Pfeiffer Friedrich
Published: July 2007

Humanoid robots are perfectly suited for service applications, since their human-like shape allows them to easily access environments designed for humans. This paper presents the performance enhanced humanoid robot LOLA. The goal of the project is to realize fast, human-like and vision-guided walking. LOLA's hardware is characterized by lightweight construction, modular, multi-sensory joint design with brushless motors and an electronics architecture using decentralized joint controllers. Real-time walking control is realized by a hierarchical trajectory generation and control system. Hardware and control are designed using a comprehensive multibody model of the robot. LOLA is equipped with a novel multi-focal vision system with four cameras and 6 degrees-of-freedom. Multifocal situation-specific gaze control provides high perception quality, flexible reaction, and accurate localization and navigation in large and weakly structured environments.