bluuebunny/crossref_metadata_2025 huggingface dataset:
Co-expression of adjacent genes in yeast cannot be simply attributed to shared regulatory system
Authors: Tsai Huai-Kuang , Su Cindy PC , Lu Mei-Yeh J , Shih Ching-Hua , Wang Daryi
Published: October 2007

Background

Adjacent gene pairs in the yeast genome have a tendency to express concurrently. Sharing of regulatory elements within the intergenic region of those adjacent gene pairs was often considered the major mechanism responsible for such co-expression. However, it is still in debate to what extent that common transcription factors (TFs) contribute to the co-expression of adjacent genes. In order to resolve the evolutionary aspect of this issue, we investigated the conservation of adjacent pairs in five yeast species. By using the information for TF binding sites in promoter regions available from the MYBS database http://cg1.iis.sinica.edu.tw/~mybs/, the ratios of TF-sharing pairs among all the adjacent pairs in yeast genomes were analyzed. The levels of co-expression in different adjacent patterns were also compared.

Results

Our analyses showed that the proportion of adjacent pairs conserved in five yeast species is relatively low compared to that in the mammalian lineage. The proportion was also low for adjacent gene pairs with shared TFs. Particularly, the statistical analysis suggested that co-expression of adjacent gene pairs was not noticeably associated with the sharing of TFs in these pairs. We further proposed a case of the PAC (polymerase A and C) and RRPE (rRNA processing element) motifs which co-regulate divergent/bidirectional pairs, and found that the shared TFs were not significantly relevant to co-expression of divergent promoters among adjacent genes.

Conclusion

Our findings suggested that the commonly shared cis-regulatory system does not solely contribute to the co-expression of adjacent gene pairs in yeast genome. Therefore we believe that during evolution yeasts have developed a sophisticated regulatory system that integrates both TF-based and non-TF based mechanisms(s) for concurrent regulation of neighboring genes in response to various environmental changes.
Mycobacterium tuberculosis 6-kDa Early Secreted Antigenic Target (ESAT-6) protein downregulates Lipopolysaccharide induced c-myc expression by modulating the Extracellular Signal Regulated Kinases 1/2
Authors: Ganguly Niladri , Giang Pham H , Basu Sandip K , Mir Fayaz Ahmad , Siddiqui Imran , Sharma Pawan
Published: October 2007

Background

Mycobacterium tuberculosis(Mtb) causes death of 2–3 million people every year. The persistence of the pathogenic mycobacteria inside the macrophage occurs through modulation of host cell signaling which allows them, unlike the other non-pathogenic species, to survive inside the host. The secretory proteins ofM. tuberculosishave gained attention in recent years both as vaccine candidates and diagnostic tools; they target the immune system and trigger a putatively protective response; however, they may also be involved in the clinical symptoms of the disease.

Results

Our studies showed that RD-1-encoded secretory protein ESAT-6 is involved in modulation of the mitogen-activated protein (MAP) kinase-signaling pathway inside the macrophage. ESAT-6 induced phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2) in the cytoplasm but not in the nucleus, which normally is the case for MAP kinases. ESAT-6 also antagonized LPS-induced ERK1/2 phosphorylation in the nucleus. Stimulation of cells by ESAT-6 along with sodium orthovanadate (a tyrosine phosphatase inhibitor) restored phosphorylation of ERK1/2 in the nucleus, suggesting active dephosphorylation of ERK1/2 by some putative phosphatase(s) in the nucleus. Further, ESAT-6 was found to down regulate the expression of LPS-inducible genec-mycin an ERK1/2-dependent manner.

Conclusion

This study showed the effect of secretory proteins ofM. tuberculosisin the modulation of macrophage signaling pathways particularly ERK1/2 MAP kinase pathway. This modulation appears to be achieved by limiting the ERK1/2 activation in the nucleus which ultimately affects the macrophage gene expression. This could be a mechanism by which secretory proteins of Mtb might modulate gene expression inside the macrophages.
Assessment of free light chains in the cerebrospinal fluid of patients with lymphomatous meningitis – a pilot study
Authors: Hildebrandt B , Müller C , Pezzutto A , Daniel PT , Dörken B , Scholz C
Published: October 2007

Background

Lymphomatous meningitis (LM) represents a severe complication of malignant lymphomas. While clinical suspicion is raised by symptoms ranging from mild disturbances of sensation to severe pain or impaired consciousness, the definite diagnosis of LM is often difficult to obtain. Since B-cell lymphomas are clonally restricted to express either kappa or lambda immunoglobulin light chain, we hypothesised that analysis of free light chain (FLC) ratios might facilitate the diagnosis of LM.

Methods

Kappa and lambda FLC were measured using a novel nephelometric assay in cerebrospinal fluid (CSF) and serum from 17 patients. 5/17 suffered from LM as demonstrated by cytology, immunocytology, and/or imaging procedures.

Results

Measurement of FLC concentrations in CSF was achieved for all 17 patients. FLC levels in CSF were lower than serum FLC levels in samples for the same patient obtained at the same time (p < 0.01). CSF and serum FLC concentrations correlated weakly in all patients irrespective of LM status. Significantly more patients with cytopathologically and immunohistochemically proven LM displayed abnormal kappa/lambda FLC ratios in CSF compared to individuals with no LM (p < 0.01).

Conclusion

This is the first report demonstrating that a significant proportion of LM patients display an abnormal kappa/lambda FLC ratio in the CSF.
A systematic approach for testing expression of human full-length proteins in cell-free expression systems
Authors: Langlais Claudia , Guilleaume Birgit , Wermke Nadja , Scheuermann Tina , Ebert Lars , LaBaer Joshua , Korn Bernhard
Published: October 2007

Background

The growing field of proteomics and systems biology is resulting in an ever increasing demand for purified recombinant proteins for structural and functional studies. Here, we show a systematic approach to successfully express a full-length protein of interest by using cell-free and cell-based expression systems.

Results

In a pre-screen, we evaluated the expression of 960 human full-length open reading frames in Escherichia coli (in vivo and in vitro). After analysing the protein expression rate and solubility, we chose a subset of 87 plasmids yielding no protein product in E. coli in vivo. These targets were subjected to a more detailed analysis comparing a prokaryotic cell-free E. coli system with an eukaryotic wheat germ system. In addition, we determined the expression rate, yield and solubility of those proteins. After sequence optimisation for the E. coli in vitro system and generating linear templates for wheat germ expression, the success rate of cell-free protein expression reached 93%.

Conclusion

We have demonstrated that protein expression in cell-free systems is an appropriate technology for the successful expression of soluble full-length proteins. In our study, wheat germ expression using a two compartment system is the method of choice as it shows high solubility and high protein yield.
Misleading pustular plaques of the lower limbs during Crohn's disease: two case reports
Authors: Farhi David , Duriez Paul , Aractingi Selim , Cosnes Jacques , Khosrotehrani Kiarash
Published: October 2007

Background

Extraintestinal manifestations of Crohn's disease may involve the skin, the eyes, the genital mucosa, and the joints. Dermatoses associated with Crohn's disease include neutrophilic dermatoses, erythema nodosum, granulomatous dermatitis, blistering dermatoses, and non-specific skin manifestations. Cutaneous Crohn's disease is characterized by skin non-caseating epithelioid granulomatas with giant cells, remote from the gastrointestinal tract. We report herein two new cases.

Observations

On both patients, differential diagnosis of neutrophilic dermatoses and infectious disease were evoked, and antimicrobial agents were introduced in one of them. Given the atypical presentation, the final diagnosis of cutaneous Crohn's disease could only be made with histological examination. In patient 1, the plaques decreased in size and infiltration by more than 75% after 3 weeks of treatment with bethametasone dipropionate 0.05% cream. In patient 2, the plaques decreased by more than 50% after 6 weeks of treatment with prednisolone (45 mg/day) and azathioprine (100 mg/day).

Discussion

Cutaneous Crohn's disease may present as dusky, erythematous, infiltrated, and ulcerated plaques and nodules. Female-to-male sex ratio is about 2, and the mean age at onset is 35. Recurrently, the hypothesis of a skin mycobacterial or fungal infection greatly delays proper treatment. Rarity of cutaneous Crohn's disease hampers therapeutic assessment in controlled trials. Thus, available literature is limited to case reports and sparse small series, with contradictory results. These reports are subject to publication bias, and no definite evidence-based recommendations can be made on the most adequate therapeutic strategy.
Assessment of Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma by Absolute Lymphocyte Counts in 2,126 Patients: 20 Years of Experience at The University of Texas M.D. Anderson Cancer Center
Authors: Tsimberidou Apostolia M. , Wen Sijin , O'Brien Susan , McLaughlin Peter , Wierda William G. , Ferrajoli Alessandra , Faderl Stefan , Manning John , Lerner Susan , Mai Chinh V. , Rodriguez Alma M. , Hess Mark , Do Kim-Anh , Freireich Emil J. , Kantarjian Hagop M. , Medeiros L. Jeffrey , Keating Michael J.
Published: October 2007

Purpose

Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are currently considered the same entity, but controversy remains over whether CLL and SLL should be treated similarly. We assessed whether characteristics of patients with CLL and SLL differ in ways other than the absolute lymphocyte count (ALC) and evaluated treatment outcomes and prognostic factors.

Methods

We searched the electronic database for patients with CLL or SLL who presented to The University of Texas M.D. Anderson Cancer Center (Houston, TX) between 1985 and 2005. We reviewed patient records to determine presenting characteristics, treatment, and clinical outcomes. Cox models using training and validation sets of patients and resampling methods were used to develop a model predicting survival.

Results

Among 2,126 consecutive CLL/SLL patients, 312 (15%) had ALC less than 5 × 109/L. Patients with ALC less than 5 × 109/L had lower rates of cytogenetic abnormalities (P = .0002) and higher rates of CD38-positive results (P = .0002) and had mutated immunoglobulin heavy-chain variable region gene status (P = .034). Rates of response, survival, and failure-free survival (FFS) were not different among ALC groups. Regimens that included rituximab and a nucleoside analog were associated with superior rates of response and FFS compared with other therapies, irrespective of ALC. Deletion 17p or 6q with or without other cytogenetic abnormalities, age at least 60 years, β2-microglobulin at least 2 mg/L, albumin less than 3.5 g/dL, and creatinine at least 1.6 mg/dL were each found to independently predict shorter survival and formed the basis of a scoring system.

Conclusion

Patients with CLL or SLL can be treated similarly. A new prognostic score is proposed.
Low-Grade Inflammation, Obesity, and Insulin Resistance in Adolescents
Authors: Herder Christian , Schneitler Sophie , Rathmann Wolfgang , Haastert Burkhard , Schneitler Heiko , Winkler Horst , Bredahl Renate , Hahnloser Erik , Martin Stephan
Published: October 2007

Context: Low-grade inflammation is associated with insulin resistance and precedes the onset of type 2 diabetes mellitus in adults, but there are no comparable data in youth.

Objective: The objective of the study was to characterize the pattern of subclinical immune activation that is associated with indices of obesity and insulin resistance in youth and analyze whether this association is explained by obesity.

Design: This was a cross-sectional study.

Setting: Medical check-up of schoolchildren was conducted by the Public Health Office in Düsseldorf (Germany).

Participants: Participants included 519 adolescents (mean age 15.5 ± 0.8 yr).

Main Outcome Measures: Measures included body mass index (BMI) and waist circumference (WC) as indices of obesity; fasting glucose, insulin, and homeostasis model assessment of insulin resistance; serum concentrations of TNFα, IL-6, IL-8, IL-18, monocyte chemoattractant protein-1, interferon-γ-inducible protein (IP)-10 and adiponectin as immunological variables.

Results: In age-, sex-, and lipid-adjusted analyses, IL-6, IL-18, IP-10, and adiponectin (inversely) were associated with both BMI and WC (all P ≤ 0.002). None of the immune markers was related to glucose, but IL-6, IL-18, and adiponectin (inversely) were associated with insulin and homeostasis model assessment of insulin resistance in age- and sex-adjusted models. Adjustment for BMI or WC indicated that a considerable proportion of these associations may be mediated by obesity.

Conclusions: We found that a differential low-grade immune activation is associated with parameters of obesity in adolescents. Moreover, there is evidence that IL-6, IL-18, IP-10, and adiponectin (inversely) are associated with insulin resistance and that these associations can mainly be attributed to obesity.
Artificial muscles based on electroactive polymers as an enabling tool in biomimetics
Authors: Bar-Cohen Y
Published: October 2007

Evolution has resolved many of nature's challenges leading to working and lasting solutions that employ principles of physics, chemistry, mechanical engineering, materials science, and many other fields of science and engineering. Nature's inventions have always inspired human achievements leading to effective materials, structures, tools, mechanisms, processes, algorithms, methods, systems, and many other benefits. Some of the technologies that have emerged include artificial intelligence, artificial vision, and artificial muscles, where the latter is the moniker for electroactive polymers (EAPs). To take advantage of these materials and make them practical actuators, efforts are made worldwide to develop capabilities that are critical to the field infrastructure. Researchers are developing analytical model and comprehensive understanding of EAP materials response mechanism as well as effective processing and characterization techniques. The field is still in its emerging state and robust materials are still not readily available; however, in recent years, significant progress has been made and commercial products have already started to appear. In the current paper, the state-of-the-art and challenges to artificial muscles as well as their potential application to biomimetic mechanisms and devices are described and discussed.
Biomimetic robotics: Self-propelled physical models test hypotheses about the mechanics and evolution of swimming vertebrates
Authors: Long J H
Published: October 2007

Biologists are beginning to combine biomimetic and robotic methods to generate and test biological hypotheses about animal function and evolution. Notable progress has been made studying aquatic vertebrate systems and their locomotor mechanisms, with self-propelled physical models improving our ability to simulate complex behavioural and mechanical systems. As biomimetic robots gain popularity as model simulations, it is essential to characterize explicitly the investigator's scientific intent and method of evaluating the robot in regards to testing hypotheses. Intent and evaluation can be characterized using Webb's seven-dimensional hyperspace for biorobotic model simulations. After reviewing this hyperspace approach, it is used to discuss three different kinds of biomimetic, swimming robots that differ in their accuracy, concreteness, and specificity with regard to their biological targets. Although each robotic system occupies a different position in Webb's hyperspace, because of the investigators' choice of biological target and method of evaluation, explicit justification of the robot's position makes it clear that no single position is better than another. Thus, biomimetic robotics is a flexible modelling methodology, addressing different kinds of biological questions and, in addition, providing engineers with plausible biological mechanisms and a library of implemented biorobotic designs.
Combustion, fire, and explosion in nature - some biomimetic possibilities
Authors: McIntosh A C
Published: October 2007

In the current paper, three areas involving fire and/or explosions in nature are explored: (a) the knobcone pine, (b) the scotch broom seed, and (c) the combustion chamber of the bombardier beetle. Each is described and some possible biomimetic applications of each of these are discussed. The knobcone pine has a high temperature controlled unique gas emission insulating system. The Scottish broom has a mechanical, humidity controlled propulsion device for dispersing its seed, and the bombardier beetle has a mass ejection system which enables the propulsion of a liquid/gas mixture to a throw ratio of 200 times its own characteristic length. The biomimetic applications in each of these examples lie in the area of fireproofing (knobcone pine), propulsion (scotch broom), and mass ejection devices such as in reigniters for gas turbines (bombardier beetle).
A Novel Method for the Deoxygenation of Sulfoxides with the PPh3/Br2/CuBr System
Authors: Bahrami Kiumars , Khodaei Mohammad Mehdi , Khedri Mohammad
Published: October 2007

It was found that the combination of PPh3/Br2/CuBr was an effective promoter for the deoxygenation of sulfoxides and gave the corresponding sulfides in excellent yield in acetonitrile under refluxing conditions. It is worth mentioning that this reagent system is chemoselective, tolerating various functional groups such as carbon–carbon double bond and ketone.
Long saphenous tunnel infiltration with levobupivicaine reduces rescue analgesia requirements following varicose vein surgery: randomized, double-blind, placebo-controlled trial [ISRCTN58431114]
Authors: Walsh S R , Waters C , Hall J , Bakar M , Boyle J , Gaunt M E
Published: October 2007

Objectives: To determine whether local anaesthetic infiltration of the long saphenous tunnel in patients undergoing unilateral, primary long saphenous stripping and multiple avulsions reduces early postoperative pain and requirement for opiate analgesia.

Methods: Patients were randomized to receive either levobupivicaine or an equivalent volume of normal saline infiltrated around the groin incision and along the long saphenous tunnel. Analgesia and linear analogue pain scores at 1, 6 and 24 h postoperatively were recorded.

Results: Fourteen patients received local anaesthetic and 13 patients received saline placebo. The anaesthetic group experienced a 22% reduction in pain scores 1 h postoperatively and a 48% reduction at 6 h although this failed to achieve statistical significance. However, the anaesthetic group were less likely to require morphine in recovery (2/14 [14%] versus 8/13 [62%]; P = 0.01). The high morphine requirements in the control group may have reduced the amount of pain those patients recorded on their pain scores and prevented statistical significance from being achieved.

Conclusion: In varicose vein surgery, local anaesthetic infiltration to the groin wound and along the full length of the stripper track is associated with reduced postoperative pain and requirements for opiate analgesia.
Assessing the gain in diagnostic performance when two visual inspection methods are combined for cervical cancer prevention
Authors: Muwonge Richard , Walter Stephen D , Wesley Ramani S , Basu Partha , Shastri Surendra S , Thara Somanathan , Mbalawa Charles Gombe , Sankaranarayanan Rengaswamy ,   The IARC Multicentre Study Group on Cervical Cancer Early Detection
Published: October 2007

Objectives: The objectives of this study was to establish whether combined screening with visual inspection with acetic acid (VIA) and Lugol's iodine (VILI) improves detection of cervical intraepithelial neoplasia 2–3 (CIN 2–3) lesions and cancer beyond chance, compared with screening with VIA alone or VILI alone; and to estimate the extra number of false-positive (FP) results per additional disease case found with the combined test, and to estimate the additional costs involved.

Setting: Ten cross-sectional studies in Burkina Faso, Congo, Guinea, India, Mali and Niger, between 1999 and 2003.

Methods: Using a common protocol, health workers screened 56,147 women aged 25–65 years with VIA and VILI. All women underwent a colposcopy examination and biopsies were taken when necessary. The disease reference standard was histology or negative colposcopy. A positive result on the combined test was defined if either VIA or VILI were positive. The accuracy of the combined test compared with VIA alone or VILI alone was evaluated using likelihood ratios.

Results: The estimated sensitivity and specificity were 81.3% and 87.3%, respectively, for VIA; 91.5% and 86.9% for VILI; and 92.9% and 83.5% for the combined test. The ratio of the positive likelihood ratios of the combined test and VIA alone for CIN 2–3 lesions and cancer was 0.88 (95% confidense interval [CI]: 0.86–0.90), favouring use of VIA alone. The ratio of the negative likelihood ratios was 0.40 (95% CI: 0.37–0.47), favouring use of the combined test. Similar results were obtained when the combined test was compared with VILI alone. Assuming equivalent performance of VIA alone and the combined test with a disease prevalence of 2%, there will be about 16.0 (95% CI: 13.6–18.8) additional FPs for each additional true positive (TP) detected if the combined test is used. This number will be 121.1 (95% CI: 75.4–194.6) if VILI is considered as the single test.

Conclusions: At the trade-off point between the combined test and VIA alone or VILI alone, given the numbers of additional FP results involved for each additional TP case of disease that were found, it would be more likely that settings already using VIA would advocate combined testing, and for settings using VILI to opt for the single test. The additional costs (per 1000 women) incurred with the combined test would be International $4117.68 versus either of the tests above.
Comparison of services provided by urban commercial, community-governed and traditional primary care practices in New Zealand
Authors: Hider Phil , Lay-Yee Roy , Crampton Peter , Davis Peter
Published: October 2007

Objectives: New Zealand has experienced restructuring and reform of primary health care since the 1980s, including the introduction of commercial clinics and increasing numbers of practices run by community-governed organizations. Our aim was to compare commercial, community-governed and traditional practices in five key domains: access; coordination and continuity of care; communication and patient centredness; population health and preventive health; and chronic disease management.

Methods: A nationally representative, multistage probability sample of private general practitioners, stratified by geographical location and practice type, was drawn. Representative samples of urban commercial clinics and of practices governed by community organizations were obtained for the same period (2001–02). All doctors were asked to provide data on themselves, their practice, and to report on a 25% sample of patients in two periods of one week.

Results: Among the three practice types, commercial clinics differed most in their organization; they charged higher fees and employed more staff, although their doctors were less experienced. Community-governed practices were visited by more people from lower socioeconomic groups. Commercial clinic patients were more likely to be younger and less likely to have an ongoing relationship with the clinic. They frequently attended for self-limiting problems related to injuries or respiratory problems. Investigations, follow-up and referral rates were similar between the three practice types. Treatment rates were higher at traditional and community-governed general practices.

Conclusion: Rather than replicating traditional practices, new practice types provide complementary services and established services in innovative ways. The challenge is to achieve an appropriate mix of diverse providers.
The cost-utility of a care coordination/home telehealth programme for veterans with diabetes
Authors: Barnett Tracey E , Chumbler Neale R , Vogel W Bruce , Beyth Rebecca J , Ryan Patricia , Figueroa Sarita
Published: October 2007

We examined the cost-effectiveness of a care coordination/home telehealth (CCHT) programme for veterans with diabetes. We conducted a retrospective, pre-post study which compared data for a cohort of veterans ( n=370) before and after the introduction of the CCHT programme for two periods of 12 months. To assess the cost-effectiveness, we converted the patients' health-related quality of life data into Quality Adjusted Life Year (QALY) utility scores and used costs to construct incremental cost-effectiveness ratios (ICERs). The overall mean ICER for the programme at one-year was $60,941, a value within the commonly-cited range of cost-effectiveness of $50,000–100,000. The programme was cost-effective for one-third of the participants. Characteristics that contributed to cost-effectiveness were marital status, location and clinically relevant co-morbidities. By targeting the intervention differently in future work, it may become cost-effective for a greater proportion of patients.
A review of seven years’ telecardiology experience
Authors: Scalvini Simonetta , Mazzù Marco , Giordano Amerigo , Zanelli Emanuela , Piemontese Carlo , Fedele Francesco , Glisenti Fulvio
Published: October 2007

We have reviewed a multidisciplinary, home-based, telecardiology service which has been used for follow-up of patients discharged early from hospital. In seven years of activity 12,576 calls have been received by 896 cardiac patients following the home based telecardiology programme: 239 patients with acute cardiac syndrome, 427 patients with chronic heart failure and 230 patients with arrhythmia. Follow-up ranged from 7–180 days. From the user's first contact with the call centre to the recording of the report took a mean time of 7–10 min. The telemedicine service is provided by a total of 14 service centre operators, 49 medical specialists, 39 nurses and 4 physiotherapists. In our experience, Web services are ideal to develop and to manage telemedicine services.
Information quality in home care coordination services
Authors: Bolt Timothy , Kano Sadahiko , Kodate Akihisa
Published: October 2007

With the increasing use of telecare, attention is being given to the information quality (IQ) issues related to the collection, storage and sharing of user data. This is particularly true for personal information and informal information flows between caregivers and care service providers. We examined data from interviews with developers and users during the pilot stage of a Web and mobile phone accessible database and software application to support carers by providing access to personal care records. The standard IQ dimensions reflect a view in which the supplier passes information to the user. This does not fully reflect the relationship and information flow in care record systems which hold and collect quite personal user data. The three additional IQ dimensions necessary are updateability, interoperability and portability — these form a new category, ‘Controllability IQ’.
Advance refusals: does the law help?
Authors: Sayers Gwen M , Kapembwa Moses S , Green Mary C
Published: October 2007

Advance refusals of life-sustaining treatment involve three potentially conflicting interests: those of the patient; those of the doctor; and those of the law. The state's interest in protecting life can clash with the patient's right to self determination which, in turn, can conflict with the doctor's desire to act in the patient's best interests. Against this background, we present the case of a patient who was treated (arguably) contrary to his advance refusal but in accordance with English law.
The legal and ethical implications of therapeutic privilege - is it ever justified to withhold treatment information from a competent patient?
Authors: Johnston Carolyn , Holt Genevieve
Published: October 2007

This article examines the standard of disclosure, set by law, of risks of treatment and alternative procedures that should normally be disclosed to patients. Therapeutic privilege has been recognized by the courts as an exception to this standard of disclosure. It provides a justification for withholding such information from competent patients in the interests of patient welfare. The article explores whether this justification is either legally or ethically defensible. In assessing patient welfare, the health care professional is required to consider the patient's overall best interests - but this is not limited to an assessment of medical best interests. It is contended that the health care professional is neither qualified nor justified in making such a judgement, as the law recognizes that a competent adult patient determines her own best interests. This is not possible without sufficient information of risks to inform the decision.
Semi-qualitative study of staff attitudes to care following decision to withdraw active treatment in a neonatal intensive care unit
Authors: Davie M , Kaiser A
Published: October 2007

The management of an infant after a decision to withdraw active treatment creates dilemmas. Both lingering death and active killing are undesirable, but palliative interventions can hasten death. We investigated what staff on our neonatal unit thought were the limits of acceptable practice and why. We administered a structured interview to elucidate their views, and asked them to justify their answers. The interviews were analysed quantitatively and qualitatively. A total of 25 participants (15 nurses and 10 doctors) were recruited. 80% emphasized the importance of pain relief following withdrawal, 60% mentioned meeting parental needs at that time. 76% agreed that death can be a desired consequence of withdrawal, yet 52% felt that death should never be hastened. 96% felt that morphine is acceptable after withdrawal, and 72% would give a higher than normal dose if necessary. 56% would stop paralysis at extubation but not reverse it, while 24% would continue paralysis. 16% would consider a drug that ended life instantly in some cases. A wide variety of views emerged, but there were two main positions, a cautious majority, and a more proactive minority. Apparent contradictions within the majority position could be explained using the doctrine of double effect and the acts and omissions distinction.
CNS-Derived Interleukin-4 Is Essential for the Regulation of Autoimmune Inflammation and Induces a State of Alternative Activation in Microglial Cells
Authors: Ponomarev Eugene D. , Maresz Katarzyna , Tan Yanping , Dittel Bonnie N.
Published: October 2007

Regulation of inflammation in the CNS is essential to prevent irreversible cellular damage that can occur in neurodegenerative diseases such as multiple sclerosis (MS). We investigated the role of interleukin-4 (IL-4) in regulating CNS inflammation using the animal model of MS, experimental autoimmune encephalomyelitis (EAE). We found that CNS-derived IL-4 was a critical regulator because mice with a deficiency in IL-4 production in the CNS, but not the periphery, had exacerbated EAE associated with a significant increase in the absolute number of infiltrating inflammatory cells. We also found that CNS-resident microglial cells in both the resting and activated state produced the protein Ym1, which is a marker of alternatively activated macrophages (aaMΦs), in an IL-4-dependent manner. This aaMΦ phenotype extended to the lack of nitric oxide (NO) production by activated microglial cells, which is a marker of classically activated macrophages. We also show that IL-4 induced the expression of Ym1 in peripheral infiltrating macrophages, which also produce NO. Thus, macrophages that migrate into the CNS exhibit a dual phenotype. These data indicate that IL-4 production in the CNS is essential for controlling autoimmune inflammation by inducing a microglial cell aaMΦ phenotype. Macrophages that have undergone alternative activation have been shown to be important in tissue repair; thus, our results suggest a new role for microglial cells in the regulation of inflammation in the CNS.
Moderate Reduction of γ-Secretase Attenuates Amyloid Burden and Limits Mechanism-Based Liabilities
Authors: Li Tong , Wen Hongjin , Brayton Cory , Laird Fiona M. , Ma Guojun , Peng Shiwen , Placanica Lisa , Wu T. C. , Crain Barbara J. , Price Donald L. , Eberhart Charles G. , Wong Philip C.
Published: October 2007

Although γ-secretase is recognized as a therapeutic target for Alzheimer's disease, side effects associated with strong inhibition of this aspartyl protease raised serious concerns regarding this therapeutic strategy. However, it is not known whether moderate inhibition of this enzyme will allow dissociation of beneficial effects in the CNS from mechanism-based toxicities in the periphery. We tested this possibility by using a series of mice with genetic reduction of γ-secretase (levels ranging from 25 to 64% of control mice). Here, we document that even 30% reduction of γ-secretase can effectively ameliorate amyloid burden in the CNS. However, global reduction of this enzyme below a threshold level increased the risk of developing squamous cell carcinoma as well as abnormal proliferation of granulocytes in a γ-secretase dosage-dependent manner. Importantly, we demonstrate that there exists a critical γ-secretase level that reduces the risk of amyloidosis in the CNS and limits tumorigenesis in epithelia. Our findings suggest that moderate inhibition of γ-secretase represents an attractive anti-amyloid therapy for Alzheimer's disease.
Estradiol Improves Cerebellar Memory Formation by Activating Estrogen Receptor β
Authors: Andreescu Corina E. , Milojkovic Bogdan A. , Haasdijk Elize D. , Kramer Piet , De Jong Frank H. , Krust Andrée , De Zeeuw Chris I. , De Jeu Marcel T. G.
Published: October 2007

Learning motor skills is critical for motor abilities such as driving a car or playing piano. The speed at which we learn those skills is subject to many factors. Yet, it is not known to what extent gonadal hormones can affect the achievement of accurate movements in time and space. Here we demonstrate via different lines of evidence that estradiol promotes plasticity in the cerebellar cortex underlying motor learning. First, we show that estradiol enhances induction of long-term potentiation at the parallel fiber to Purkinje cell synapse, whereas it does not affect long-term depression; second, we show that estradiol activation of estrogen receptor β receptors in Purkinje cells significantly improves gain-decrease adaptation of the vestibulo-ocular reflex, whereas it does not affect general eye movement performance; and third, we show that estradiol increases the density of parallel fiber to Purkinje cell synapses, whereas it does not affect the density of climbing fiber synapses. We conclude that estradiol can improve motor skills by potentiating cerebellar plasticity and synapse formation. These processes may be advantageous during periods of high estradiol levels of the estrous cycle or pregnancy.
Paradoxical Upregulation of Glutamatergic Presynaptic Boutons during Mild Cognitive Impairment
Authors: Bell Karen F. S. , Bennett David A. , Cuello A. Claudio
Published: October 2007

Synaptic integrity is now recognized as a central component of Alzheimer's disease. Surprisingly, however, the structural status of glutamatergic synapses in Alzheimer's disease is unclear, despite the fact that glutamate is the major excitatory transmitter of the CNS and has key roles in excitotoxicity and long-term potentiation. The identification of specific markers of glutamatergic neurons now allows an assessment of the structural involvement of the glutamatergic system across progressive stages of the Alzheimer's pathology, an opportunity not afforded by previously used neurochemical approaches. Glutamatergic presynaptic bouton density and dystrophic neurite abundance were quantified in midfrontal gyrus brain tissue from subjects with no cognitive impairment, mild cognitive impairment, or mild- or severe-stage Alzheimer's disease. Our study demonstrates a striking pathology-dependent pattern of glutamatergic synaptic remodeling with disease progression. Subjects with mild cognitive impairment display a paradoxical elevation in glutamatergic presynaptic bouton density, a situation akin to that observed in the cholinergic system, which then depletes and drops with disease progression. This pattern of synaptic remodeling mirrors our previous findings in transgenic animal models and is of major relevance to current transmitter-based therapeutics.
Book Reviews
Authors: DOOSTDAR ALIREZA
Published: October 2007

Warring Souls: Youth, Media, and Martyrdom in Post‐Revolution Iran. Roxanne Varzi. Durham, NC: Duke University Press, 2006. xiv + 290 pp., photographs, references, index.
Designing a Brave New World: Eugenics, Politics, and Fiction
Authors: WOIAK JOANNE
Published: October 2007

Aldous Huxley composed Brave New World in the context of the Depression and the eugenics movement in Britain. Today his novel is best known as satirical and predictive, but an additional interpretation emerges from Huxley's nonfiction writings in which the liberal humanist expressed some surprising opinions about eugenics, citizenship, and meritocracy. He felt that his role as an artist and public intellectual was to formulate an evolving outlook on urgent social, scientific, and moral issues. His brave new world can therefore be understood as a serious design for social reform, as well as a commentary about the social uses of scientific knowledge.
Deadly Medicine
Authors: BACHRACH SUSAN
Published: October 2007

This article discusses the methods the United States Holocaust Memorial Museum used to make an exhibition on the complex history of Nazi eugenics accessible to the museum's mass public and at the same time, provocative for special audiences consisting of professionals and students from the biomedical fields. Deadly Medicine: Creating the Master Race showed how both eugenics and related “euthanasia” programs in Nazi Germany helped pave the road to the Holocaust. The exhibition implicitly evoked the present-day appeal of biological explanations for human behavior and of new visions of human perfection. Educational programs used the exhibition as a springboard for discussions of bioethics and medical ethics.
Chasing Aleck: The Story of a Dorm
Authors: EDWARDS R. A. R.
Published: October 2007

A student raised a hand in class and asked, “Why is this dorm named after Alexander Graham Bell?” On a deaf campus, this was a loaded question. Bell was an oralist, opposed to sign language. He was a eugenicist, opposed to deaf marriages. Indeed, the more I thought about it, the better this question got. Why did the school name a dorm after him? Unfortunately, I hadn't the foggiest idea. With apologies to that student, I offer this article as a belated answer.
Hereditarily Lindelöf spaces of singular density
Authors: Juhász István , Shelah Saharon
Published: October 2007

A cardinal
λ
is called
ω
-inaccessible if for all µ <
λ
we have µ
ω
<
λ
. We show that for every
ω
-inaccessible cardinal
λ
there is a CCC (hence cardinality and cofinality preserving) forcing that adds a hereditarily Lindelöf regular space of density
λ
. This extends an analogous earlier result of ours that only worked for regular
λ
.
Quantifying evidence in forensic authorship analysis
Authors: Grant Tim
Published: October 2007

The judicial interest in ‘scientific’ evidence has driven recent work to quantify results for forensic linguistic authorship analysis. Through a methodological discussion and a
worked example this paper examines the issues which complicate attempts to quantify results in work. The solution suggested to some of the difficulties is a sampling and
testing strategy which helps to identify potentially useful, valid and reliable markers of authorship. An important feature of the sampling strategy is that these markers identified as being generally valid and reliable are retested for use in specific authorship analysis cases. The suggested approach for drawing quantified conclusions combines discriminant function analysis and Bayesian likelihood measures. The worked example starts with twenty comparison texts for each of three potential authors and then uses a progressively smaller comparison corpus, reducing to fifteen, ten, five and
finally three texts per author. This worked example demonstrates how reducing the amount of data affects the way conclusions can be drawn. With greater numbers of
reference texts quantified and safe attributions are shown to be possible, but as the number of reference texts reduces the analysis shows how the conclusion which should be reached is that no attribution can be made. The testing process at no point results in instances of a misattribution.
Non-contemporary speech samples: auditory detectability of an 11 year delay and itseffect on automatic speaker identification
Authors: Künzel Hermann J.
Published: October 2007

The need to compare non-contemporary speech samples is a common issue in forensic speaker recognition. Even if the size of the delay is known a crucial question has still to be
answered in every single case: Is it possible that physiological aging or other factors have caused alterations of parameters of voice, speech and language to such a degree that the material basis for identification by human listeners and/or by automatic systems may no longer be regarded as adequate when a new identification task is due? Some studies on auditory speaker recognition suggest that, other variables being equal, a time lag of up to 6 years does not seem to pose a problem. To this author’s knowledge, the question has not yet been directed towards automatic identification systems. The present study uses speech
data from ten male speakers recorded at intervals of 11 years and analyses the effect of the delay in terms of (a) the ability of different groups of listeners to detect it, and (b) its
influence on the performance of an advanced automatic speaker identification system for forensic applications. Using contemporary samples for both ‘known’ and ‘unknown’
models as a benchmark the automatic speaker identification system identified all speakers correctly with LRs between 102 and over 108. In the non-contemporary condition,
where the older samples (i.e. ‘younger’ speakers) were used for the construction of models for ‘known’ and the samples recorded 11 years later for ‘unknown’ speakers, LRs of nine
speakers remained unchanged or dropped only slightly. The LR for one speaker dropped sharply. It seems that this is the only case in which vocal aging, but perhaps also other
time-related factors, may have played a rôle. The main conclusions of these experiments are that for most male speakers a delay of the size of a decade between voice samples will not pose a problem to either auditory or machine-based speaker identification.
Forensic automatic speaker recognition using Bayesian interpretation and statistical compensation for mismatched conditions
Authors: Alexander Anil
Published: October 2007

Awarding Institution: Ecole Polytechnique Fédérale de Lausanne (EPFL),
Switzerland

Date of Award: November 2005
‘Speak English or what?’ Codeswitching and interpreter use in New York Small Claims Courts
Authors: Angermeyer Philipp Sebastian
Published: October 2007

Awarding Institution: New York University, USA

Date of Award: May 2006
Examining jurors’ discursive exchanges related to mitigating factors during capital jury deliberations
Authors: Cassar Desiree
Published: October 2007

Awarding Institution: The Graduate School and University Center of The City
University of New York, USA

Date of Award: May 2005
Linguistic Manipulations in Legal Discourse: Framing questions and ‘smuggling’ information*
Authors: Aldridge Michelle , Luchjenbroers June
Published: October 2007

With an emphasis on the linguistic experiences of sexual-assault witnesses in the British legal system (adult rape victims and child abuse victims), this paper is a
consideration of how the lexical choices in the questions posed to a witness encourage a particular perception of her testimony. The concepts to be discussed include conceptual
frames and smuggling information, and we offer a qualitative consideration of how the semantic features of a lawyer’s lexical choices can support a representation of either
the witness or her experiences that is not in her interests. The appropriateness of a lawyer’s chosen frame is of key importance to ‘smuggling information’, a term used
when a lawyer’s question inserts (negative) information into a witness’s testimony through suggestion. We look at how such linguistic manipulations can weaken a
witness’s account by suggesting that she is to blame, and/or is lying or perhaps has simply misunderstood the situation. Our analysis offers an explanation as to why vulnerable witnesses may not be believed in court.
Merton’s True Self and the Psychology of the Dialogical Self
Authors: Pembroke Neil
Published: October 2007

Thomas Merton pursued a life-long quest to grasp the nature of the “true self.” This is the self that lives in and through Christ. Opposed to this is the false self that is expressive of infidelity. It is argued that the interaction between the true and false selves constitutes a dialogical process. The thesis of the essay is that this interaction expresses the dynamics associated with what some psychologists refer to as the “dialogical self.” The dialogical self is a model of the inner life that draws attention to the interpretive process required to deal with the many voices that get internalized in an engagement with the world
Brian Morris. Religion and Anthropology: A Critical Introduction
Authors: Rodriques Hillary
Published: October 2007

Brian Morris. Religion and Anthropology: A Critical Introduction. Cambridge: Cambridge University Press, 2006. x + 350 pp. pbk ISBN: 0-521-61779-0. $27.00 US.
Erratum
Authors: Waugh Earle
Published: October 2007

.
Cromoblastomicose no Rio Grande do Sul: relato de 12 casos
Authors: Matte Shirley M.W. , Lopes Jorge O. , Melo Ivanir S. , Espadim Luís Eduardo R. , Pinto Marcelo Souza
Published: October 2007

São relatados 12 casos de cromoblastomicose diagnosticados no interior do Rio Grande do Sul, no período 1988-1995. Os aspectos clínicos e evolutivos são analisados e comparados com a literatura. O único agente isolado foi Fonsecaea pedrosoi.
Zigomicose nasofacial no Estado do Pará: registro de dois casos
Authors: Moraes Mário A.P. , Arnaud Maria Vanda Catão , Almeida Margarida Maria R.
Published: October 2007

São descritos dois casos de zigomicose nasofacial, procedentes de Belém, PA. O achado indica não ser tão rara, como se poderia supor, pela falta de registros, a ocorrência dessa micose na Região Norte do Brasil. Em ambos os pacientes, o tratamento pelo cetoconazol determinou involução rápida das manifestações clínicas, principalmente a obstrução nasal. Com o presente relato, sobe para cinco o número de casos da infecção referidos até agora do Estado do Pará.
Os problemas do fundacionismo
Authors: Burdzinski Júlio César
Published: October 2007

Este trabalho analisa o fundacionismo epistemológico, uma das principais alternativas de resposta ao problema do regresso epistêmico. Em particular, o autor pretende sistematizar aquelas que entende serem as dificuldades básicas que a proposta fundacionista deve superar para resolver satisfatoriamente o problema do regresso. Para tanto, acompanha as duas vertentes principais pelas quais circula o fundacionismo contemporâneo, a saber, a vertente internalista e a vertente externalista. Nesse acompanhamento, as noções de "justificação epistêmica" e de "crença básica" são prioritariamente avaliadas.