bluuebunny/crossref_metadata_2025 huggingface dataset:
Nitric oxide and histamine signal attempts to swallow: A component of learning that food is inedible inAplysia
Authors: Katzoff Ayelet , Miller Nimrod , Susswein Abraham J.
Published: December 2009

Memory that food is inedible inAplysiaarises from training requiring three contingent events. Nitric oxide (NO) and histamine are released by a neuron responding to one of these events, attempts to swallow food. Since NO release during training is necessary for subsequent memory and NO substitutes for attempts to swallow, it was suggested that NO functions during training as a signal of attempts to swallow. However, it has been shown that NO may also be released in other contexts affecting feeding, raising the possibility that its role in learning is unrelated to signaling attempts to swallow. We confirmed that NO during learning signals attempts to swallow, by showing that a variety of behavioral effects on feeding of blocking or adding NO do not affect learning and memory that a food is inedible. In addition, histamine had effects similar to NO on learning that food is inedible, as expected if the transmitters are released together when animals attempt to swallow. Blocking histamine during training blocked long-term memory, and exogenous histamine substituted for attempts to swallow. NO also substituted for histamine during training. Histamine at concentrations relevant to learning activates neuron metacerebral cell (MCC). However, MCC activity is not a good monitor of attempts to swallow during training, since the neuron responds equally well to other stimuli. These findings support and extend the hypothesis that NO and histamine signal efforts to swallow during learning, acting on targets other than the MCC that specifically respond to attempts to swallow.
Endogenous cannabinoids trigger the depolarization-induced suppression of excitation in the lateral amygdala
Authors: Kodirov Sodikdjon A. , Jasiewicz Julia , Amirmahani Parisa , Psyrakis Dimitrios , Bonni Kathrin , Wehrmeister Michael , Lutz Beat
Published: December 2009

The amygdala is a key area of the brain where the emotional memories are stored throughout the lifespan. It is well established that synapses in the lateral nucleus of amygdala (LA) can undergo long-term potentiation, a putative cellular correlate of learning and memory. However, a type of short-term synaptic plasticity, known as depolarization-induced suppression of excitation (DSE), has not been studied previously in the amygdala in general and in the LA in particular. In this study we aimed to prove either the absence or the presence of this phenomenon in the LA. Our data demonstrate for the first time that DSE is present in the LA and that it modulates the cortical excitatory synaptic input into this region. The existence of this type of retrograde neurotransmission in glutamatergic pyramidal neurons of the LA suggests that the axonal terminals of cortical inputs do possess functional type 1 cannabinoid receptors, and provides a novel insight regarding inputs into the LA. Further experiments indeed revealed endocannabinoids as the messenger for this retrograde signaling in the LA. In conclusion, the DSE may play a functional role in synaptic plasticity and related emotional memory processing in the LA.
Anti‐miR‐21 oligonucleotide sensitizes leukemic K562 cells to arsenic trioxide by inducing apoptosis
Authors: Li Yumin , Zhu Xuejiao , Gu Jingyi , Dong Dawei , Yao Junlin , Lin Chunyan , Huang Kangkang , Fei Jia
Published: January 2010

Arsenic trioxide (ATO), an ancient traditional Chinese medicine, has been successfully used as a therapeutic agent for leukemia. Drug resistance and toxicity are major concerns with the treatment. MicroRNAs (miRNAs) are endogenous small non‐coding RNA molecules that might modulate cellular sensitivity to anticancer drugs. miRNA‐21 (miR‐21) is one of the most prominent miRNAs involved in various aspects of human cancers. However, miR‐21 has been rarely characterized in chronic myelogenous leukemia (CML). Here, we used a specific anti‐miR‐21 oligonucleotide (AMO‐miR‐21) to sensitize K562 cells to ATO by degradation of miR‐21. The results showed that both AMO‐miR‐21 and ATO caused growth inhibition, apoptosis, and G1‐phase arrest in K562 cells. Meanwhile, AMO‐miR‐21 significantly promoted ATO‐mediated growth inhibition and apotosis without affecting the G1 phase. Apoptotic cells were confirmed morphologically with Giemsa’s staining. Furthermore, dual‐luciferase reporter vector, containing two tandem miR‐21 binding sites from PDCD4 3′UTR, validated that PDCD4 was directly regulated by miR‐21. Therefore, AMO‐miR‐21 sensitized leukemic K562 cells to ATO by inducing apoptosis partially due to its up‐regulation of PDCD4 protein level. The combination of ATO and AMO‐miR‐21 present therapeutic potential for CML.

(Cancer Sci 2010; 101: 948–954)
Field evaluation of a decision support system for herbicidal control of Avena sterilis ssp. ludoviciana in winter wheat
Authors: GONZALEZ‐ANDUJAR J L , FERNANDEZ‐QUINTANILLA C , BASTIDA F , CALVO R , GONZALEZ‐DIAZ L , IZQUIERDO J , LEZAUN J A , PEREA F , SANCHEZ DEL ARCO M J , URBANO J M
Published: January 2010

Gonzalez‐Andujar JL, Fernandez‐Quintanilla C, Bastida F, Calvo R, Gonzalez‐Diaz L, Izquierdo J, Lezaun JA, Perea F, Sanchez Del Arco MJ & Urbano JM (2010). Field evaluation of a decision support system for herbicidal control of Avena sterilis ssp. ludoviciana in winter wheat. Weed Research50, 83–88.

Two field studies were conducted in Central and Northern Spain over a total of five seasons to assess the usefulness of a decision support system (AVENA‐PC) from agronomic, economic and environmental points of view on herbicidal control of Avena sterilis ssp. ludoviciana in winter wheat. The control treatments evaluated were: (i) AVENA‐PC‐based recommendations, (ii) full herbicide dose (standard farmer practice), (iii) half herbicide dose and (iv) no herbicide. The herbicide rates used in the AVENA‐PC treatment averaged 65% and 30% lower than the full and half dose treatments respectively. AVENA‐PC implementation controlled A. ludoviciana with similar efficacy as standard herbicide treatments. Nevertheless, it did support a reduction in relation to the non‐herbicide treatment. Yields obtained with AVENA‐PC were, in general, not statistically different to those obtained with herbicide treatments and were on average 69% higher than those in the no herbicide application strategy. Comparing AVENA‐PC economic performance with the other treatments there were, in general, no significant statistical differences in Central Spain. In Northern Spain, all herbicide treatments had similar net returns, with there being no statistical differences between AVENA‐PC and the herbicide treatments. However, there were differences recorded with the non‐herbicide treatment. The results of this research indicate that AVENA‐PC, due to its flexibility, may recommend less herbicide than the standard farmer practice, providing clear environmental benefits and adequate weed control with maintained crop yield and net returns similar to standard farmer practice.
Risk factors for pneumonia caused by multidrug‐resistant Gram‐negative bacilli among liver recipients
Authors: Shi Shao Hua , Kong Hai Shen , Jia Chang Ku , Zhang Wen Jin , Xu Jian , Wang Wei Lin , Shen Yan , Zhang Min , Zheng Shu Sen
Published: December 2009

Shi SH, Kong HS, Jia CK, Zhang WJ, Xu J, Wang WL, Shen Y, Zhang M, Zheng SS. Risk factors for pneumonia caused by multidrug‐resistant Gram‐negative bacilli among liver recipients.  Clin Transplant 2010: 24: 758–765. © 2009 John Wiley & Sons A/S.

Abstract:  Pneumonia caused by multidrug‐resistant (MDR) Gram‐negative bacilli is associated with a higher mortality rate. The appropriate empiric therapy is based on the understanding of local etiology and MDR pattern. This study was to evaluate the spectrum of Gram‐negative bacilli, MDR rate, risk factors and mortality in 475 liver transplantation (LT) recipients. In the first six months after LT, the incidence of bacterial pneumonia was 21.3% (101/475). The overall infectious incidence during the first post‐transplant month was 80.2%. The most frequent pneumonia isolates were Enterobacteriaceae, Acinetobacter baumannii, Pseudomonas aeruginosa and Staphylococcus aureus. Gram‐negative bacilli accounted for 69.6% of all pneumonia pathogens. Of the main 124 Gram‐negative bacilli isolates, MDR rate was 58.9%. Four risk factors for post‐LT pneumonia caused by MDR Gram‐negative bacilli were LT candidates with grade II–IV encephalopathy (OR 2.275, 95%CI 1.249–4.124, p = 0.006), prolonged duration of endotracheal intubation (OR 8.224, 95%CI 4.276–15.815, p = 0.013), tracheostomy (OR 4.929, 95%CI 1.099–18.308, p = 0.027) and post‐LT episode(s) of reoperations (OR 10.597, 95%CI 3.726–30.134, p < 0.001). MDR Gram‐negative bacterial pneumonia‐related mortality was significantly higher than that because of antibiotic‐susceptible bacilli (45.6% vs. 11.4%, p = 0.010). Our data suggest that pneumonia caused by MDR Gram‐negative bacilli after LT is common, and associated with the severity of underlying disease, prolonged mechanical ventilation and upper abdominal surgery.
An exploration of participation in leisure activities post‐stroke
Authors: O’Sullivan Clare , Chard Gill
Published: December 2009

Aim: The purpose of this study was to illuminate the experiences of older adults’ return to leisure activities, following rehabilitation, post‐stroke.

Method: A phenomenological approach was used to explore the experiences of re‐engaging in leisure occupations post‐stroke. In‐depth interviews were conducted with five community‐dwelling individuals (three men, two women) aged 68–74 years who had experienced a stroke in the past year. Data were analysed using thematic analysis.

Findings: Four themes emerged: (i) Re‐engaging in leisure activities, (ii) acceptance of physical limitations post‐stroke, (iii) gratitude for help and support and (iv) looking forward to the future.

Conclusion: Implications revealed that post‐stroke interventions need a more occupation‐focussed approach, including return to leisure at an earlier stage of stroke rehabilitation.
Genetic content in Korean nursing textbooks
Authors: Kim Miyoung , Han Jinho
Published: December 2009

Due to the significant developments in genetic health services that have occurred, nurses now must strive to incorporate cutting‐edge information from this fast‐evolving field into their day‐to‐day practice. This study examined the amount and the content of genetics education in Korean nursing textbooks. We analyzed 165 textbooks that were published by four companies between 2005 and 2009. Eighty percent contained some information on genetics; however, the content was limited to bioscience, the latest information on common diseases, and nursing interventions in genetics. There was an average of six pages of genetics content in the seven specialized textbooks on nursing that were analyzed. This indicates that many topics on genetics need to be incorporated into Korean nursing education, especially in light of the recent genetic innovations in all curricular areas of nursing education. We recommend the establishment of strategic perspectives to bridge the content gaps in genetics education in nursing.
Obtaining confirmation through social relationships: Norwegian first‐time mothers' experiences while on maternity leave
Authors: Alstveit Marit , Severinsson Elisabeth , Karlsen Bjørg
Published: December 2009

The social relationships of employed women on maternity leave undergo significant changes. The aim of the study was to illuminate first‐time mothers' experiences of social relationships while on maternity leave. Nine mothers were interviewed at both 3–5 months and 11–14 months post‐partum and the data were analyzed by means of interpretative analysis. The main theme of obtaining confirmation through social relationships was based on two themes (being confirmed by other mothers and balancing between being a mother and an employee) and on four subthemes (seeking company, sharing experiences, feeling ineffective and in a state of stagnation, and trying to handle contact with the workplace). In order to strengthen the social relationships of mothers, the mother–child health service should offer all mothers the opportunity to join a peer support group, while employers could keep in regular contact with staff members on maternity leave.
Developing practice in mental health settings
Authors: Cleary Michelle , Horsfall Jan , Happell Brenda
Published: January 2010

If practice development (PD) is to be implemented in diverse mental health‐care settings, it is important that managers, researchers, and policy makers are all clear about the nature of the processes involved. The authors draw on the literature to broadly set out local strategies, practicalities, and issues that should be considered and addressed by those planning to undertake PD projects in mental health. Before implementing PD projects, pre‐existing requirements should be recognized and expedited. All aspects of who does what, when, and how should be widely communicated so that continuous evaluation and improvements are generated. Staff need to be adult learners, be aware of their practice values, be able to access supervision, and confront contradictions and tensions between values and practice. PD programmes that are effective are built into mainstream activities, considered core business, utilize existing resources to build sustainable and realistic improvements, take direction from practitioners, and incorporate client needs.
What constitutes a ‘Good’ recovery outcome in post‐acute Guillain–Barré syndrome? Results of a Nationwide Survey of post‐acute GBS sufferers in the United Kingdom
Authors: Davidson I. , Wilson C. , Walton T. , Brissenden S. , Campbell M. , McGowan L.
Published: December 2009

Background:  Eighty percent of people with Guillain–Barré Syndrome (GBS) are said to achieve ‘good’ outcome. ‘Good’ outcome has been defined as either of the top two scores (0 = Healthy, 1 = minor symptoms or signs, able to run) on a 7‐point ordinal scale called the F‐score. This assessment of ‘good’ outcome appears to be an arbitrary benchmark. This study is the first assessment of the differences in outcome between post‐acute GBS sufferers reporting these scores. It attempts to compare the physical and emotional differences between respondents reporting ‘0’ and ‘1’ on the F‐Score.

Methods:  A postal survey was administered to respondents through the UK Guillain–Barré Syndrome Support Group’s national database and included items relating to general patient data, general mobility, F‐Score, Hospital Anxiety and Depression Scale, SF 36 and Fatigue Severity Scale.

Results:  One thousand five hundred and thirty‐five members were surveyed, and of 884/1535 (58%) questionnaires were returned. Results indicate significant differences between those scoring ‘0’ on the F‐Score and those scoring ‘1’ in the post‐acute phase in terms of anxiety, depression, physical functioning, fatigue and wheelchair use on discharge.

Conclusions:  Significantly poorer outcomes for those scoring ‘1’ on the F‐Score suggest that only those scoring ‘0’ should constitute a ‘good’ outcome in GBS.
How are we doing with the treatment of essential tremor (ET)?
Authors: Louis E. D. , Rios E. , Henchcliffe C.
Published: January 2010

Background:  The pharmacological treatment of essential tremor (ET) is not optimal. There are only two first‐line medications and troublesome side effects are common. It is not uncommon for patients to simply stop taking medication. Yet, no published data substantiate or quantify this anecdotal impression.

Objectives:  To determine, amongst patients with ET who were prescribed medication for tremor, what proportion are still taking medication and what proportion have stopped?

Methods:  Five hundred and twenty‐eight patients with ET from three distinct study settings (clinical, brain donors, population) were interviewed.

Results:  A clear pattern that emerged across settings was that the proportion of patients with ET who had stopped medication was sizable and consistently similar (nearly one‐third): 31.4% (clinical), 24.3% (brain donors), 30.0% (population), 29.8% (overall). A similarly high proportion of cases with severe tremor had stopped their medication: 31.9% (clinical), 36.4% (brain donors). For the four most commonly used medications (propranolol, primidone, diazepam, topiramate), one‐half or more of the treated patients had stopped the medication; amongst the less commonly used medications, the proportion who stopped was even higher.

Conclusions:  Nearly one of every three patients with ET who had been prescribed medication for tremor had discontinued pharmacotherapy. Even more revealing was that a similar proportion of cases with severe tremor had stopped medication. These data make tangibly evident that there is a sizable population of patients with ET who are untreated and disabled, and underscore the inadequacy of current pharmacotherapeutic options for this common neurological disease.
Theological Exegesis as Exegetical Showing: A Case of Isaiah's Figural Potentiality
Authors: GIGNILLIAT MARK
Published: January 2010

Theological exegesis demands engagement with the biblical text. Much of the current discussion regarding this topic tends to remain in the realm of theory and method without much ‘exegetical showing’. Taking a cue from Brevard Childs' understanding of the Old Testament as Christian Scripture, this article provides an example of theological exegesis with Isaiah as the focus text. The intertextual relationship between Isaiah 6 and 61 is engaged in its literary/canonical fixity. From this fixity, the figural potentiality of this intertextual relationship is explored in light of the two‐testament canon and its shared subject matter.
Bioethics and the Samoan indigenous reference
Authors: Tui Atua Tupua Tamasese Ta'isi Efi
Published: January 2010

Bioethical questions are of primary concern to science, religion and traditional or indigenous knowledge. What the indigenous reference can offer the world is a re‐appreciation of the rightful place of the spiritual, sacred and tapu (implicit in indigenous cultural rituals) in ethical debates. This article explores what might be the ethical in the Samoan indigenous reference. Two main indigenous Samoan concepts, tapu (the sacred) and tofa sa'ili (the search for wisdom), are considered and situated in contemporary Samoan experiences and understandings of the ethical. If ethics is about moral principles or values, these two Samoan concepts provide the basis for ethical research in a Samoan indigenous context. This article aims at providing a Samoan frame of reference to deliberate about universal codes for bioethical research and the nature of ethical research practice in the Pacific.
Group IIA secretory phospholipase A2(GIIA) mediates apoptotic death during NMDA receptor activation in rat primary cortical neurons
Authors: Chiricozzi Elena , Fernandez‐Fernandez Seila , Nardicchi Vincenza , Almeida Angeles , Bolaños Juan Pedro , Goracci Gianfrancesco
Published: January 2010

J. Neurochem.(2010)112, 1574–1583.

Phospholipases A2(PLA2) participate in neuronal death signalling pathways because of their ability to release lipid mediators, although the contribution of each isoform and mechanism of neurotoxicity are still elusive. Using a novel fluorogenic method to assess changes in a PLA2activity by flow cytometry, here we show that the group IIA secretory phospholipase A2isoform (GIIA) was specifically activated in cortical neurons following stimulation ofN‐methyl‐d‐aspartate glutamate receptor subtype (NMDAR). For activation, GIIA required Ca2+and reactive oxygen/nitrogen species, and inhibition of its activity fully prevented NMDAR‐mediated neuronal apoptotic death. Superoxide, nitric oxide or peroxynitrite donors stimulated GIIA activity, which mediated neuronal death. Intriguingly, we also found that GIIA activity induced mitochondrial superoxide production after NMDAR stimulation. These results reveal a novel role for GIIA in excitotoxicity both as target and producer of superoxide in a positive‐loop of activation that may contribute to the propagation of neurodegeneration.
Glycosaminoglycan‐induced activation of the β‐secretase (BACE1) of Alzheimer’s disease
Authors: Klaver David W. , Wilce Matthew C. J. , Gasperini Robert , Freeman Craig , Juliano John Paul , Parish Christopher , Foa Lisa , Aguilar Marie‐Isabel , Small David H.
Published: January 2010

J. Neurochem. (2010) 112, 1552–1561.

The β‐site APP cleaving enzyme (BACE1) is responsible for the first step in the production of the β‐amyloid protein of Alzheimer’s disease. BACE1 is synthesized as a partially active zymogen (proBACE1). We previously showed that the glycosaminoglycan (GAG) heparin can increase the enzyme activity of proBACE1. In this study, the structural requirements and the mechanism for the GAG‐induced activation were examined. The effect of heparin on proBACE1 was influenced by the degree of sulfation and carboxylation of the GAG, as well as by the length of the sugar. Although low molecular weight heparin fragments did not strongly stimulate proBACE1, they inhibited heparin‐induced activation of the enzyme. The structure of the zymogen was modeled using the known X‐ray structures of the BACE1 catalytic domain and the homologous prodomain of porcine pepsinogen. The modeled structure suggested that a heparin‐binding domain may reside close to the prodomain, and that movement of a loop region between residues 46–65, lying adjacent to the prodomain, may be needed to accommodate heparin binding. The presence of the loop domain adjacent to the active site may account for the lower activity of the zymogen relative to the mature enzyme. Movement of the loop region upon heparin binding could expose the active site region to allow for increased substrate binding. The results suggest a model in which conformational changes close to the prodomain may be involved in the mechanism of heparin‐induced activation of proBACE1.
Does the Frequency of Pay‐for‐Performance Payment Matter?—Experience from a Randomized Trial
Authors: Chung Sukyung , Palaniappan Latha , Wong Eric , Rubin Haya , Luft Harold
Published: December 2009

Objective. To examine the effects of incentive payment frequency on quality measures in a physician‐specific pay‐for‐performance (P4P) experiment.

Study Setting. A multispecialty physician group practice.

Study Design. In 2007, all primary care physicians (n=179) were randomized into two study arms differing by the frequency of incentive payment, either four quarterly bonus checks or a single year‐end bonus (maximum of U.S.$5,000/year for both arms).

Data Collection/Extraction Methods. Data were extracted from electronic health records. Quality measure scores between the two arms over four quarters were compared.

Principal Findings. There was no difference between the two arms in average quality measure score or in total bonus amount earned.

Conclusions. Physicians' responses to a P4P program with a small maximum bonus do not differ by frequency of bonus payment.
Effects of Two Amphibian Pathogens on the Developmental Stability of Green Frogs
Authors: ST‐AMOUR VALÉRIE , GARNER TRENTON W.J. , SCHULTE‐HOSTEDDE ALBRECHT I. , LESBARRÈRES DAVID
Published: January 2010

Abstract:  Developmental instability, measured as fluctuating asymmetry (FA), is often used as a tool to measure stress and the overall quality of organisms. Under FA, it is assumed that control of symmetry during development is costly and that under stress the trajectory of development is disturbed, resulting in asymmetric morphologies. Amphibian emergent infectious diseases (EIDs), such as Ranavirus and chytrid fungus, have been involved in several mortality events, which makes them stressors and allows for the study of FA. We analyzed nine populations of green frogs (Rana clamitans) for the presence or absence of Ranavirus and chytrid fungus. Individuals were measured to determine levels of FA in seven traits under the hypothesis that FA is more likely to be observed in individuals infected by the pathogens. Significantly higher levels of FA were found in individuals with Ranavirus compared with uninfected individuals among all populations and all traits. We did not observe FA in individuals infected with chytrid fungus for any of the traits measured. Additionally, we observed a significant association between Ranavirus infection and levels of FA in both males and females, which may indicate this viral disease is likely to affect both sexes during development. Altogether, our results indicate that some EIDs may have far‐reaching and nonlethal effects on individual development and populations harboring such diseases and that FA can be used as a conservation tool to identify populations subject to such a stress.
Dentistry students’ perceptions of learning management systems
Authors: Handal B. , Groenlund C. , Gerzina T.
Published: January 2010

This paper reports an exploratory survey study about students’ perceptions of learning management systems (LMS) at the Faculty of Dentistry, University of Sydney. Two hundred and fifty‐four students enrolled in the Bachelor of Dentistry and the Bachelor of Oral Health programmes participated in an online survey aimed at exploring their beliefs and attitudes as well as their preferences for eLearning tools. Results indicated a strong preference of students for using LMSs as resource repositories rather than for higher‐order learning activities such as online discussion forums. This finding holds importance for consideration of the development of the educational resources modalities that support development of essential graduate attributes such as information literacy and collaborative learning.
Predicting dental school performance based on prior dental experience and exposure
Authors: Park S. E. , Da Silva J. D. , Barnes J. L. , Susarla S. M. , Howell T. H.
Published: January 2010

Purpose:  The purpose of this study was to evaluate whether the variables of students with prior dental assisting experience and students with a parent who is a dentist can be used as predictors of students’ pre‐clinical and clinical course performance in dental school.

Materials and methods:  The study population consisted of a cohort of 159 students in the Harvard School of Dental Medicine (HSDM) DMD graduation classes of 2001—2005. Data were collected via self‐report using students’ applications for admission to the HSDM DMD programme on which students provided information regarding whether they had prior dental assisting experience, including the type and duration of the experience and whether one or both of their parents were dentists. Data on the students’ undergraduate science grade point average, Dental Admission Test academic average, Perceptual Ability Test (PAT) score, NBDE Part I and HSDM course grades (three pre‐clinical and five clinical assessment categories) were collected from the Office of the Registrar. The pre‐clinical categories included the first Oral Comprehensive Exam and the first two classes of the pre‐clinical portion of the dental school, Treatment of Active Disease (TxAD) and Restorative Treatment (RTx). The clinical categories included the second Oral Comprehensive Exam and the cumulative grades received for the clinical procedures performed during the third and fourth years in the fields of Endodontics, Operative Dentistry, Periodontics and Prosthodontics. Descriptive and bivariate statistical analyses were performed and included in a multiple logistic regression model.

Results:  The results revealed that for the variable of prior dental‐assisting experience, no statistically significant differences were noted in the pre‐clinical and clinical assessment categories. However, students who had any amount of assisting experience were 2.2 times more likely to earn a grade of honours in TxAD compared with students who did not have assisting experience (P = 0.05). Students with a parent who was a dentist performed better only in Operative Dentistry clinical assessment compared with students without a dentist parent (P < 0.05).

Conclusions:  Information on prior dental‐assisting experience and having a parent who is a dentist have minimal merits for use as predictive agents based on these findings. Dental school admissions committees should continue to review a full spectrum of variables and ensure an applicant’s true interest and motivation to pursue a career in dentistry.
Intrinsic GTPase activity of a bacterial twin‐arginine translocation proofreading chaperone induced by domain swapping
Authors: Guymer David , Maillard Julien , Agacan Mark F. , Brearley Charles A. , Sargent Frank
Published: January 2010

The bacterial twin‐arginine translocation (Tat) system is a protein targeting pathway dedicated to the transport of folded proteins across the cytoplasmic membrane. Proteins transported on the Tat pathway are synthesised as precursors with N‐terminal signal peptides containing a conserved amino acid motif. In Escherichia coli, many Tat substrates contain prosthetic groups and undergo cytoplasmic assembly processes prior to the translocation event. A pre‐export ‘Tat proofreading’ process, mediated by signal peptide‐binding chaperones, is considered to prevent premature export of some Tat‐targeted proteins until all other assembly processes are complete. TorD is a paradigm Tat proofreading chaperone and co‐ordinates the maturation and export of the periplasmic respiratory enzyme trimethylamine N‐oxide reductase (TorA). Although it is well established that TorD binds directly to the TorA signal peptide, the mechanism of regulation or control of binding is not understood. Previous structural analyses of TorD homologues showed that these proteins can exist as monomeric and domain‐swapped dimeric forms. In the present study, we demonstrate that isolated recombinant TorD exhibits a magnesium‐dependent GTP hydrolytic activity, despite the absence of classical nucleotide‐binding motifs in the protein. TorD GTPase activity is shown to be present only in the domain‐swapped homodimeric form of the protein, thus defining a biochemical role for the oligomerisation. Site‐directed mutagenesis identified one TorD side‐chain (D68) that was important in substrate selectivity. A D68W variant TorD protein was found to exhibit an ATPase activity not observed for native TorD, and an in vivo assay established that this variant was defective in the Tat proofreading process.

Structured digital abstract

MINT‐7302371, MINT‐7302377: TorD (uniprotkb:P36662) and TorD (uniprotkb:P36662) bind (MI:0407) by molecular sieving (MI:0071)

MINT‐7302402: TorD (uniprotkb:P36662) and TorD (uniprotkb:P36662) bind (MI:0407) by comigration in non denaturing gel electrophoresis (MI:0404)

MINT‐7302387: TorD (uniprotkb:P36662) and TorD (uniprotkb:P36662) bind (MI:0407) by cosedimentation in solution (MI:0028)
Electrophysiological Characterization of Isolated Human Atrial Myocytes Exposed to Tegaserod
Authors: Suffredini Silvia , Cerbai Elisabetta , Giunti Gabriele , El Mouelhi Mohamed , Pfannkuche Hans‐Jürgen , Mugelli Alessadro
Published: December 2009

Abstract: Tegaserod (Teg), a 5‐hydroxytryptamine type‐4 (5‐HT4) receptor partial agonist, represents a novel treatment for irritable bowel syndrome with constipation and chronic constipation. Cardiovascular safety data from pooled clinical studies showed a signal suggestive of increased occurrence of ischaemic cardiovascular events in patients exposed to Tegversusplacebo. Thereafter, marketing of Teg was suspended in the USA and other countries. The clinical data did not demonstrate a causative effect but raised questions of whether a non‐recognized effect on the heart was present. Our aim was to evaluate for arrhythmogenic potential of Teg on human cardiomyocytes. Cells isolated from human atrial specimens during cardiac surgery were used to assess the effects of Teg (1, 10, 30 and 100 nM) on action potential andIf(funny current) by patch‐clamp technique. Results showed that Teg (at all concentrations tested) did not significantly affect action potential characteristics of atrial myocytes when driven at different rates (0.2, 0.5 and 1 Hz). In contrast, 5HT significantly prolonged action potential duration (1 and 10 nM) and caused cell un‐excitability (100 nM). Teg, at the highest concentration tested (100 nM, corresponding to 10 timesCmax, produced by the recommended dose of 6 mg b.i.d.) increased theIfamplitude and caused a shift of its activation curve. This effect of a high concentration of Teg is not considered clinically relevant. When evaluated on single human atrial cells, Teg does not appear to exhibit arrhythmogenic properties, as it did not affect the action potential profile.
Amelioration of Oxaliplatin Neurotoxicity by Drugs in Humans and Experimental Animals: A MiniReview of Recent Literature
Authors: Ali Badreldin H.
Published: December 2009

Abstract:  The broad spectrum anti‐neoplastic drug oxaliplatin is a third‐generation platinum compound that inhibits DNA synthesis, mainly by causing intrastrandal cross‐links in DNA. The drug is particularly useful alone and in combination with flurouracil and leucovorin in colorectal cancer, but it is also used for other cancers such as those of the ovary, lung, breast and liver, as well as non‐Hodgkin’s lymphoma. The drug is known to cause neurological, gastrointestinal and haematological toxicities. Neurotoxicity occurs in most of the treated patients and is considered to be a serious limitation for the use of the drug. The mechanism of the neurotoxicity is not known with certainty but may involve prolongation of sodium channels opening. Strategies to ameliorate oxaliplatin neurotoxicity include the use of several ‘neuroprotective’ drugs. This MiniReview attempts to list and comment on the action and use of some of these agents, which include carbamazepine, gabapentin, calcium and magnesium salts, reduced glutathione, N‐acetylcysteine and a few others. None of these drugs have been proven to be effective in large, controlled, clinical trials.
Active‐Site Concentrations of Chemicals – Are They a Better Predictor of Effect than Plasma/Organ/Tissue Concentrations?
Authors: Hammarlund‐Udenaes Margareta
Published: December 2009

Abstract: Active‐site concentrations can be defined as the concentrations of unbound, pharmacologically active substances at the site of action. In contrast, the total concentrations of the drug in plasma/organ/tissue also include the protein‐ or tissue‐bound molecules that are pharmacologically inactive. Plasma and whole tissue concentrations are used as predictors of effects and side effects because of their ease of sampling, while the concentrations of unbound drug in tissue are more difficult to measure. However, with the introduction of microdialysis and subsequently developed techniques, it has become possible to test the free drug hypothesis. The brain is an interesting organ in this regard because of the presence of the blood‐brain barrier with its tight junctions and active efflux and influx transporters. We have proposed that research into brain drug delivery be divided into three main areas: the rate of delivery (PS, CLin), the extent of delivery (Kp,uu) and the non‐specific affinity of the drug to brain tissue, described by the volume of distribution of unbound drug in the brain (Vu,brain). In this way, the concentration of unbound drug at the target site can be estimated from the total brain concentration and the plasma concentration after measuring the fraction of unbound drug. Results so far fully support the theory that active site concentrations are the best predictors when active transport is present. However, there is an urgent need to collect more relevant data for predicting active site concentrations in tissues with active transporters in their plasma membranes.
Russell, His Paradoxes, and Cantor's Theorem: Part II
Authors: Klement Kevin C.
Published: January 2010

Sequel to Part I. In these articles, I describe Cantor's power‐class theorem, as well as a number of logical and philosophical paradoxes that stem from it, many of which were discovered or considered (implicitly or explicitly) in Bertrand Russell's work. These include Russell's paradox of the class of all classes not members of themselves, as well as others involving properties, propositions, descriptive senses, class‐intensions and equivalence classes of coextensional properties. Part II addresses Russell's own various attempts to solve these paradoxes, including strategies that he considered and rejected (limitation of size, the zigzag theory, etc.), as well as his own final views whereupon many purported entities that, if reified, lead to these contradictions, must not be genuine entities, but ‘logical fictions’ or ‘logical constructions’ instead.
Colonisation credit in recent wet heathland butterfly communities
Authors: CRISTOFOLI SARA , MAHY GRÉGORY
Published: December 2009

Abstract.  1. Wet heathlands and closely associated habitats (e.g. bogs and poor fens) have been highly fragmented over the last two centuries. These habitats nowadays benefit from large‐scale restoration projects, for which the success should be evaluated.

2. Recently, the concept of colonisation credit (the number of species yet to colonise a patch) was proposed as a spatially explicit framework to assess recovery in species richness following restoration. In this study, we estimated the colonisation credit of wet heathland butterfly communities in Southern Belgium. The method was applied separately to generalist and specialist species for two reference dates (new patches <25 years old and new patches 25–55 years old).

3. Only a marginally significant colonisation credit was detected for generalist species. In contrast, we found a significant colonisation credit for specialists, although this was due to a very limited number of strict specialist species. Butterfly community composition differed only marginally between patch age classes.

4. As a general trend, butterfly communities exhibit a rapid response (<25 years) to landscape structure modification. However, conservation and restoration actions should urgently target strict specialists, exhibiting colonisation limitation in new habitat patches. A lack of colonisation credit for plant communities in the same landscape suggests that restoration of wet heathlands may be successful in the short term for various taxonomic groups.
Vibratory Power Losses and Delivery to Rock During Rotary-Vibratory Drilling: Part II, Application
Authors: Mitchell L. D. , Ohanehi D. C.
Published: January 2010

This paper applies the theoretical solution developed in Part 1 of this paper to a rotary-vibratory drilling unit. The theory developed and applied in these papers explains possible causes for the failures of such devices to perform properly in the vertical vibratory mode. This paper predicts improved performance based upon system design changes. Power delivery as a function of depth is studied. Power delivery problems at great depths are uncovered. Further system redesign is suggested. The redesign implementation in the model results in recovery of the power delivery capability to the rock.
Extension of the Transfer Matrix Method for Rotordynamic Analysis to Include a Direct Representation of Conical Sections and Trunnions
Authors: Darlow M. S. , Murphy B. T. , Elder J. A. , Sandor G. N.
Published: January 2010

The transfer matrix method for rotordynamic analysis (alternately known as the HMP or LMP method) has enjoyed wide popularity due to its flexibility and ease of application. A number of computer programs are generally available which use this method in various forms to perform undamped critical speed, unbalance response, damped critical speed and stability analyses. For all of these analyses, the assembly of the transfer matrices from the rotor model is essentially the same. In all cases, the rotor model must be composed entirely of cylindrical beam elements. There are two situations when this limitation is not desirable. The first situation is when the rotor being modelled has one or more sections whose cross sections vary continually in the axial direction. The most common of these sections is the conical section. Presently, a conical section must be modelled as a series of “steps” of cylindrical sections. This adversely affects both the simplicity and accuracy of the rotor model. The second situation when current transfer matrix techniques are not accurate is when the rotor being modelled has one or more sections that do not behave as beam elements. The most common example is a trunnion which behaves as a plate. This paper describes the analytical basis and the method of application for direct representation of conical sections and trunnions for a transfer matrix analysis. Analytical results are currently being generated to demonstrate the need for and advantages of these modelling procedures.
The Control of Structural Vibration by Frictional Damping in Electro-Discharge Machined Joints
Authors: Beards C. F. , Neroutsopoulos A. A.
Published: January 2010

EDM joints are attractive for use in structures because the machining operation is cheap and easy to perform, while producing joints with good conformity of interface. It is shown that EDM joints have high static and dynamic stiffness and possess up to 100 percent more damping capacity than ground joints, while surface damage due to fretting corrosion is reduced by an order of magnitude. For all joints tested, the fretting action caused an increase in the damping and a decrease in the dynamic stiffness, the maximum variations being 60 percent and 5 percent respectively, after 107 cycles.
Moderately Large Amplitude Plate Vibration Modes
Authors: Kennedy J. C.
Published: January 2010

The influence of moderately large amplitudes on the frequency of vibration for the fundamental mode and some higher modes of the simply supported rectangular plate is established. Plate equations that are valid for the moderately large motions are programmed for solution on the analog computer. The effect of eliminating in-plane motions and accelerations on the system response is quantitatively established. It is shown that frequency ratio versus amplitude ratio is aspect ratio dependent and the study shows how simplifying assumptions made in some previous studies affect this dependence.
Accurate Reduction of Stiffness and Mass Matrices for Vibration Analysis and a Rationale for Selecting Master Degrees of Freedom
Authors: Downs B.
Published: January 2010

A method is described which permits the reduction of stiffness and mass matrices on to selected degrees of freedom, while accurately retaining, up to a certain cut-off frequency, the dynamic characteristics of the original matrices. The validity of the method is demonstrated by obtaining identical results, for the reduction of a simple system, with those derived from a rigorous solution. An interpolation equation is also developed which allows the eigenvector components on the eliminated degrees of freedom to be determined accurately from the ‘master’ components. Some guidelines are provided for the optimal selection of the ‘master’ degrees of freedom and a procedure defined for progressively improving the initial selection, prior to undertaking the eigenvalue analysis.
Application of Dynamic Programming to Optimize Tool Replacement Schedules for Multi-Tool Operations Involving Distributed Tool Lives
Authors: Bao H.
Published: January 2010

There have been a number of models developed to provide the optimum tool replacement schedule for a multi-tool set-up. However, most of these models are quite complex and are geared to yield solutions for a very large set-up involving an indefinite number of parts. In this paper a new tool replacement model aimed at a machining process involving a moderate number of tools (2 to 6) and a discrete number of parts (50 to 100) is developed based on the technique of Dynamic Programming. Tool lives in the set-up are assumed to be distributed.
A Sufficient Test for Global Optimality with Signomial Design Applications
Authors: McNeill B. , Wilde D.
Published: January 2010

A general, sufficient test for proving a local minimum to be the global minimum is presented. The test uses a special lower bounding function and methods for constructing this special bounding function for univariable or multivariable unconstrained signomial design problems are given. Two simple design problems illustrate the use of the constructions and test.
A Graphic Man-Computer Environment for Three Dimensional Engineering Design
Authors: Brewer J. A. , Anderson D. C.
Published: January 2010

An interactive computer graphics system for three dimensional design is described. The system combines the speed, accuracy and accessibility of a relatively low-cost minicomputer and refresh display with versatile and powerful interactive software to achieve a truly effective environment for visual design of complex three dimensional data. The designer creates and manipulates objects interactively using several convenient input devices that communicate his commands to the system and move a shaping tool on the display screen. Several example design sequences are included to illustrate various features of the system. An application to finite element mesh generation is also discussed.
The Utility of Nonlinear Programming Algorithms: A Comparative Study—Part I
Authors: Sandgren E. , Ragsdell K. M.
Published: January 2010

A comprehensive comparative study of nonlinear programming algorithms, as applied to problems in engineering design, is presented. Linear approximation methods, interior penalty and exterior penalty methods were tested on a set of thirty problems and are rated on their ability to solve problems within a reasonable amount of computational time. In this paper we discuss the organization and conduct of the study, and in a companion paper, we give numerical results and algorithm performance curves.
The Utility of Nonlinear Programming Algorithms: A Comparative Study—Part II
Authors: Sandgren E. , Ragsdell K. M.
Published: January 2010

A comprehensive comparative study of nonlinear programming algorithms, as applied to problems in engineering design, is presented. Linear approximation methods, interior penalty and exterior penalty methods were tested on a set of thirty problems and are rated on their ability to solve problems within a reasonable amount of computational time. In this paper, we give and discuss numerical results and algorithm performance curves.
Digitizing for Computer-Aided Finite Element Model Generation—Part 1: The General Program
Authors: Kamel H. A. , Navabi Z.
Published: January 2010

Computer-aided design is a complex process involving many disciplines. This two part paper describes an approach to computer-aided design which has evolved for the specific discipline of structural analysis. The vehicle for the implementation of the approach is a collection of programs called the GIFTS system. The first part of the paper describes the latest version of GIFTS. The second part of the paper will discuss a digitizing program aimed at facilitating the preparation of input defining complex two-dimensional models for the GIFTS mesh generator.
Vibration Analysis of Turbomachinery Blades Using Dedicated Discretization and Twisted Beam Theory
Authors: Downs B.
Published: January 2010

A method of discretizing the stiffness and mass properties of beam segments of turbine or compressor blades is presented. The theory encompasses both the modification of beam bending and torsional stiffnesses due to pretwist and the coupling of bending and torsional deformation with axial deformation occasioned by pretwist. Examples show that accurate prediction of vibration frequencies for blades possessing substantial pretwist can be obtained by discretization on to a quite modest number of degrees of freedom. Some comparisons of prediction accuracy with Finite Element and other methods are included.