bluuebunny/crossref_metadata_2025 huggingface dataset:
Intracerebral Hemorrhage: Outcomes and Eligibility for Factor VIIa Treatment in a National Stroke Registry
Authors: Nadeau Janel O. , Phillips Stephen , Shi HaiJiang S. , Kapral Moira K. , Gladstone David J. , Silver Frank L. , Hill Michael D.
Published: June 2006

Background: Intracerebral hemorrhage (ICH) is a devastating form of stroke for which the lack of treatment options, high mortality rate, and the tendency to severely disable result in high social and economic burden. Methods: We analyzed data in the Registry of the Canadian Stroke Network (RCSN). We sought to: (1) provide a descriptive analysis of ICH; (2) determine the proportion of ICH patients that might have been eligible for treatment with recombinant activated factor VII (rFVIIa) using criteria from a recent phase II trial; (3) compare 6-month outcomes of ICH patients with those of ischemic stroke patients, matched for gender, age, and stroke severity. Results: In the RCSN, 11% of all strokes were nontraumatic ICH. The median Canadian Neurological Scale score was 7. A minority (33%) of patients arrived to the emergency department in less than 3 h from onset. In this cohort, in-hospital mortality was 15%. At 6 months, a further 9% of patients had died and 58% had a slight to no disability (Stroke Impact Scale-16 score ≧75). Approximately 20% of ICH patients would have been eligible for rFVIIa treatment. Compared to ischemic stroke, ICH showed a trend towards increased mortality at discharge (OR: 1.96, CI: 0.99–3.87). At 6-month follow-up, ICH showed increased mortality (OR: 2.27, CI: 1.29–3.97), yet functional outcomes were not significantly different. Conclusion: ICH patients had a higher case-fatality rate when compared to acute ischemic stroke, but survivors had similar functional outcomes. In Canada, about one fifth of ICH patients might potentially benefit from rFVIIa if it is approved, with the major exclusion factor being time.
Comparative Evaluation of the Effects of Unilateral Lesion versus Electrical Stimulation of the Globus Pallidus Internus in Advanced Parkinson’s Disease
Authors: Jiménez Fiacro , Velasco Francisco , Carrillo-Ruiz José D. , García Luis , Madrigal Adrián , Velasco Ana Luisa , Márquez Irma
Published: June 2006

Objective: To perform a prospective analysis on the effects of unilateral lesion versus unilateral electrical stimulation (ES) of the globus pallidus internus (Gpi) in the treatment of bilateral Parkinson’s disease (PD). Materials and Methods: We studied 18 patients with stages III–V on the Hoehn and Yahr (H-Y) scale having prominent rigidity, bradykinesia and gait disturbances. Nine patients were treated with lesions and 9 patients with ES. Both groups were evaluated using the New York Parkinson’s Disease Scale, the Unified Parkinson’s Disease Rating Scale part III, and the H-Y scale and with specific items of tremor, rigidity and bradykinesia independently on each side. Both lesions and electrodes for ES were placed stereotactically in the Gpi as confirmed by postoperative magnetic resonance images. Significance of changes was evaluated with the Wilcoxon test after 3 and 6 months. Significance of intergroup differences was evaluated using the Mann-Whitney U test. Results: Lesions and ES significantly decreased rigidity (p < 0.01) and bradykinesia (p < 0.005) in the contralateral extremities. ES significantly decreased tremor in the contralateral extremities (p < 0.01) and rigidity and bradykinesia ipsilaterally (p < 0.01) at 3 months. There were no significant intergroup differences. The H-Y scale score showed improvement in self-sufficiency. L-DOPA dose was decreased by 31%. Conclusions: ES was a safer procedure and more efficient in controlling PD symptoms. Unilateral lesions and ES may improve bilateral symptoms to the point of making patients self-sufficient.
Gene Expression Profiles on Hypoxia and Reoxygenation in Rat Gastric Epithelial Cells: A High-Density DNA Microarray Analysis
Authors: Katada Kazuhiro , Naito Yuji , Mizushima Katsura , Takagi Tomohisa , Handa Osamu , Kokura Satoshi , Ichikawa Hiroshi , Yoshida Norimasa , Matsui Hirofumi , Yoshikawa Toshikazu
Published: June 2006

Previous investigations have demonstrated that the cellular signaling induced by hypoxia-reoxygenation is a major pathway contributing to gastric mucosal injury induced by stress, non-steroidal anti-inflammatory drugs, and Helicobacter pylori. The aim of the present study was to perform a gene expression analysis of the gastric mucosal cellular response and to define the protective molecules in hypoxia and reoxygenation using a high-density DNA microarray analysis. Normal rat gastric mucosal (RGM-1) cells were subjected to hypoxia for 2 h, and reoxygenation was initiated by placing the cells in an environment of normoxia for 2, 4, or 8 h. Total RNA was extracted, and differences in the gene expression profiles between the normoxia and hypoxia groups or among the different durations of reoxygenation were investigated using a high-density DNA microarray. HIF-1- and apoptosis-related genes were modulated by hypoxia. Moreover, inflammation-, stress-, and wound- healing-related genes were regulated by reoxygenation following hypoxia. In particular, the expression of heat shock protein-70, amphiregulin and cyclooxygenase-2 were upregulated during reoxygenation following hypoxia, suggesting that these upregulations may play an important role in maintaining cell survival and supporting cell function.
Britain and Dissent in Tito’s Yugoslavia: The Djilas Affair, ca. 1956
Authors: Djokić Dejan
Published: June 2006

This work sheds light on British official and unofficial responses to the ‘Djilas affair’ in its early stages. The analysis is centred around two letters written in April 1956 - by Milovan Djilas to Morgan Phillips, the Labour Party Secretary, and a letter Phillips wrote to the Yugoslav President Tito, expressing his concern for Djilas’ predicament. The article contributes to a better understanding of the Djilas affair in several ways. Djilas’ letter offers a good insight into both his character and the predicament in which he found himself 2 years after the conflict with the Yugoslav leadership began and only 7 months before he was first arrested. Phillips’ action reveals that some leading members of the Labour Party were prepared to act on Djilas’ behalf. The governing Conservative Party, on the other hand, was more concerned with keeping good relations with Belgrade than with the destiny of the first significant dissident in Eastern Europe
Market Reforms and Psychological Distress in Urban Beijing
Authors: Lai Gina , Lee Rance P. L.
Published: June 2006

This article examines the change in psychological well-being among urban residents in Beijing, China, over a 10-year period of rapid social change. The findings suggest that urban reforms generate economic gains at the expense of urban residents’ psychological well-being. Results from two community surveys conducted in 1991 and 2000 reveal that urban Beijing residents have experienced greater life stress and a rise in depressive symptoms during the 10-year period. The decline in psychological well-being between 1991 and 2000 can be partly explained by greater exposure of Beijing residents to life stressors in the course of rapid social changes associated with the urban reforms. The survey results also lend support to the social adjustment and stress explanation, but not the social relations and support explanation. Changes in social relations only marginally affect the change in depressive symptomatology, and the protective function of social relations, particularly relations with family and co-workers, has gained importance over the years.
Socially Constructed Ethnic Division of Labour
Authors: Kung I-chun , Wang Hong-zen
Published: June 2006

Using fieldwork data from Taiwanese-owned factories in Malaysia and Vietnam, the authors argue that the labour regime based on ethnic division of labour is a function of the degree of proletarianization, which depends on the state's policies and one's social capital. State policy protects native Malay and Vietnamese, and excludes the rights of migrant workers, regardless of whether these migrant workers are skilled or unskilled. Local ethnic Chinese, with higher social capital, find themselves somewhere between the two poles.
Polemics with Enochic Traditions in the Exagoge of Ezekiel the Tragedian
Authors: Ruffatto Kristine J.
Published: June 2006

The Exagoge, Ezekiel the Tragedian’s second-century BCE drama about the Exodus, contains a non-biblical account of Moses’ vision of God’s throne on Sinai. This apocalyptic merkavah vision reveals that Enochic traditions were formative in Ezekiel’s writing. In the Exagoge, Ezekiel attributes to Moses what had earlier been claimed for Enoch. In presenting Moses as the patriarch who ascends and receives esoteric revelation on Sinai, Ezekiel is establishing the primacy of Moses and his revelation. In the drama, Moses not only ascends and has a merkavah vision: he is divinized. This elevation of Moses is a challenge to accounts of an exalted Enoch. This article provides an analysis of the role of Ezekiel’s drama in Enochic-Mosaic polemics. The Exagoge exalts Moses over Enoch, founding Moses’ superlative status upon his ascent, vision, received revelation, and deification on Sinai.
The Physician as Political Actor: Late Abortion and The Strictures of Liberal Moral Discourse
Authors: Brock Brian , Wyatt John
Published: June 2006

By examining the range of factors pressing on medical professionals faced with a decision in a case of late-term abortion, it becomes apparent that the theological resources ruled out of bounds by the standard account can be considered an essential part of a truly liberating and properly supple moral account of medical decision-making. Close attention to the social, political and legal context of contemporary medicine reveals that the standard account of medical ethics, Principles of Biomedical Ethics by Beauchamp and Childress, despite its universalist aspirations, disempowers rather than empowers moral decision-making by medical professionals.
Putting Truth To Practice: Macintyre's Unexpected Rule
Authors: Hovey Craig
Published: June 2006

It is difficult to exaggerate Alasdair MacIntyre's influence on contemporary Christian ethics. Under his influence, many have sought to show the distinctive features of a Christian account of the virtues, even while discovering that they have needed to go further than MacIntyre himself does. In an attempt to illustrate why some Christian ethicists and theologians have noted MacIntyre's reluctance to follow through on some of his own projects’ most salient aspects, this article examines his 1994 lectures on truthfulness and lying. In particular, I ask why he unexpectedly proposes a rule that suffers from Kantian abstraction. Even though articulating rules can be a crucial task, Christian ethics can often do better. Rather than search for a rule or even practices that require truthfulness, I suggest instead that Christian witness be explored as itself a truth-telling practice.
Eros and Ethics: Levinas's Reading of Plato's ‘Good Beyond Being’
Authors: Webb Mary-Ann
Published: June 2006

This paper addresses the notorious logic and semantic difficulties encountered by Lévinas in articulating his ethics of alterity. Tracing the philosophical genesis of this question in Descartes and Heidegger, it recognises Lévinas's claim that there can be no ontological foundation for ethics because ontology would reduce ethics to a form of mathematical ratio. Lévinas is unwilling to deny his phenomenological experience of a desire for goodness and unable to deny his despair at his ontological alienation from the good and so he is driven to seek an irrational link between the human being and a metaphysical ‘good beyond being’. Retrieving an ancient gnostic neo-Platonist working of the same problem from the work of Hans Jonas, the paper reconsiders Lévinas's reading of Plato, specifically his understanding of Socrates’ exposition of erosin the Phaedo, in order to illustrate how his ethics of alterity may allow the human being to refer irrationally to the good beyond being.
Higher standards, better schools for all – a critique: can market forces close the social and achievement gap?®
Authors: Merrett Gena
Published: June 2006

The government's White Paper published earlier this year has clear aims for improving schools, in particular: to address the attainment gap between the high and low achieving schools; and to address the fact that a child's educational achievements are still too strongly linked to their parents’ social and economic background – a key barrier to social mobility. This article sets out to dispute that the government will improve schools, or address the attainment gap between high and low achieving schools or improve social mobility through the policies they propose to implement – in particular, transporting low SES students to higher SES schools, expanding higher SES schools and closing urban ‘failing’ schools. The article uses recent school improvement research from a number of sources to emphasize the impact of social background on school improvement. It sets out, with reference to a number of researchers, the enduring nature of social values on educational achievements and the way in which market forces have actually widened the gap between high and low achieving schools with little impact on overall student achievement.
Collaborative consultation training: the missing link to the enhancement of collaborative relationships among education and mental health professionals®
Authors: Cochrane Wendy S. , Salyers Kathleen M.
Published: June 2006

The ability of education and mental health professionals to collaborate is essential when providing services to children and adolescents. It is imperative, therefore, that professionals from different theoretical orientations understand collaborative consultation as the basis for developing effective working relationships. The purpose of this article is to provide information on collaborative consultation in education and mental health professions as it exists in the United States and its impact upon the provision of these services. It also serves as an information resource on collaborative consultation for the international community. University training designed to ensure an understanding of the process and purpose of collaborative consultation will be addressed. The article concludes with suggested coursework and student teaching/internship activities designed to develop this competency
Developing frameworks for school self evaluation to improve school effectiveness for peace in Northern Ireland®
Authors: Smith Ron , Neill June
Published: June 2006

Against a background of slow progress towards a more peaceful and plural society in Northern Ireland, the research reported in this article describes the efforts of two Northern Irish democratic educators to develop user-friendly tools that help educational practitioners undertake a deep scrutiny of everything that makes up institutional life in order to improve learning-teaching for intercommunal relations. The views of students, parents and teachers on what makes an effective school for peace formed the starting point for this work. Following a brief contextualization and review of influential research, the new frameworks and tools emerging from the research are shared: the ‘Institutional Map for Peace with Social Justice’ (I-MAP); the ‘School Peacebuilding Index’ (SPI) and the ‘Dual-axis Organizational Analysis for Inter-School Contact’ (Da-ORG).
Developing a quality assurance metric
Authors: Love Steve , Scoble Rosa
Published: June 2006

There are a variety of techniques that lecturers can use to get feedback on their teaching - for example, module feedback and coursework results. However, a question arises about how reliable and valid are the content that goes into these quality assurance metrics. The aim of this article is to present a new approach for collecting and analysing qualitative feedback from students that could be used as the first stage in developing more reliable quality assurance metrics. The approach, known as the multi-dimensional crystal view, is based on the belief that individuals have different views on the benefits that the embedded process in a system can have on the behaviour of the system. The results of this study indicate that in the context of evaluation and feedback methods, the multi-dimensional approach appears to provide the opportunity for developing more effective student feedback mechanisms.
Contrasting views of induction
Authors: Staniforth David , Harland Tony
Published: June 2006

This article focuses on the induction experiences of new academic staff and the role of their head of department in this process. Respondents reflected on personal experiences and their narratives give a fine-grained account of the same event from two contrasting perspectives. We expected to find that the heads would be key figures in the induction process, but we discovered a more complex situation in which contributions were largely hidden or indirect. We encountered many contradictions as each party recalled events. Meaningful communication had been sporadic at best, and professional and personal relationships were left undeveloped. In all cases, there was little genuine understanding of the potential of induction, and this was particularly evident in the lack of personal action displayed by the new academics. Some heads had developed a deeper theoretical position on induction but few of their ideas were realized in practice. We propose that this was mainly due to the heads’ lack of experience and because induction outcomes were not systematically evaluated.
The Rise and Fall of Species-Life
Authors: Gershenson Geoffrey
Published: June 2006

Rousseau’s founding critique of liberalism, the Discourse on the Origin of Inequality, takes the ambiguous form of a sweeping myth of civilization. Political theorists usually interpret the myth by reading it as a tale of passage from primordial nature to civil society, but what happens when we privilege another of the essay’s organizing devices, its symbolic depiction of the history of the species as the life of an individual? Interpreted through this metaphor, Rousseau’s myth becomes a charged tale of a ‘life’ gone wrong, one that sheds interesting light on his critique of bourgeois society and selfhood
Robust Alternatives and Responsibility
Authors: Allen Robert
Published: June 2006

The Principle of Robust Alternatives (PRA) states that an agent is responsible for doing something only if he/she could have performed a ‘robust’ alternative: another action having a different moral or practical value. Defenders of PRA maintain that it is not refuted by a ‘Frankfurt case’, given that its agent can be seen as having had such an alternativeprovided that we properly qualify that for which she is responsible. I argue here against two versions of this defense. First, I show that those who maintain that a ‘Frankfurt agent’ is responsible forvoluntarily performing his/her action must attach moral significance to his/her luck. I proceed to discuss Carl Ginet's strategy of temporally qualifying ascriptions of responsibility, arguing that his counterexample to the principle that ‘If an agent is responsible for doing A @ t, then he/she is responsible for doing Asimpliciter’ is disanalogous to a Frankfurt case.
Rorty, the First Amendment and Antirealism: Is Reliance upon Truth Viewpoint-Based Speech Regulation?
Authors: Butler Brian
Published: June 2006

In this article I investigate the implications of antirealism, as characterized by Richard Rorty, for First Amendment jurisprudence under the United States Constitution. It is hoped that the implications, while played out in the context of a specific tradition, will have more universal application. In Section 1, Rorty’s ‘pragmatic antirealism’ is briefly outlined. In Section 2, some effects of the elimination of the concept of truth for First Amendment jurisprudence are investigated. Section 3 argues for the conclusion that given the antirealist stance, the Supreme Court’s usage of the true/ false fact distinction is actually an uncritical allowance of viewpoint-based discrimination into speech protection that has potentially far-reaching and restrictive results for important speech. Finally, in Section 4 Rorty’s antirealism is combined with various traditional models of First Amendment analysis to see how it would function. The conclusions aimed at are twofold. First, that Rortian antirealism is compatible with the traditional models underlying First Amendment theory. Second, that a realization that truth is the result of, in Rorty’s words, ‘intra-mundane’ discourse leads to an argument for different and potentially stronger and more farreaching protections to speech.
Bruton tyrosine kinase is essential for botrocetin/VWF-induced signaling and GPIb-dependent thrombus formation in vivo
Authors: Liu Junling , Fitzgerald Malinda E. , Berndt Michael C. , Jackson Carl W. , Gartner T. Kent
Published: June 2006

Botrocetin (bt)-facilitated binding of von Willebrand factor (VWF) to the platelet membrane glycoprotein (GP) Ib-IX-V complex on platelets in suspension initiates a signaling cascade that causes αIIbβ3 activation and platelet aggregation. Previous work has demonstrated that bt/VWF-mediated agglutination activates αIIbβ3 and elicits ATP secretion in a thromboxane A2 (TxA2)-dependent manner. The signaling that results in TxA2 production was shown to be initiated by Lyn, enhanced by Src, and propagated through Syk, SLP-76, PI3K, PLCγ2, and PKC. Here, we demonstrate that the signaling elicited by GPIb-mediated agglutination that results in TxA2 production is dependent on Bruton tyrosine kinase (Btk). The results demonstrate that Btk is downstream of Lyn, Syk, SLP-76, and PI3K; upstream of ERK1/2, PLCγ2, and PKC; and greatly enhances Akt phosphorylation. The relationship(s), if any, between ERK1/2, PLCγ2, and PKC were not elucidated. The requirement for Btk and TxA2 receptor function in GPIb-dependent arterial thrombosis was confirmed in vivo by characterizing blood flow in ferric chloride-treated mouse carotid arteries. These results demonstrate that the Btk family kinase, Tec, cannot provide the function(s) missing because of the absence of Btk and that Btk is essential for both bt/VWF-mediated agglutination-induced TxA2 production and GPIb-dependent stable arterial thrombus formation in vivo.
Impact of chronic graft-versus-host disease on the health status of hematopoietic cell transplantation survivors: a report from the Bone Marrow Transplant Survivor Study
Authors: Fraser Christopher J. , Bhatia Smita , Ness Kirsten , Carter Andrea , Francisco Liton , Arora Mukta , Parker Pablo , Forman Stephen , Weisdorf Daniel , Gurney James G. , Baker K. Scott
Published: June 2006

The aim of this study was to understand the impact of chronic graft-versus-host disease (cGVHD) on the overall health status of hematopoietic cell transplantation (HCT) survivors. Subjects included 584 individuals who had undergone allogeneic HCT between 1976 and 1999, survived 2 or more years, and completed a 255-item health questionnaire. Global assessment of health status was facilitated by measurement of 6 health status domains: general health, mental health, functional impairment, activity limitation, pain, and anxiety/fear. Information regarding diagnosis of cGVHD was abstracted from medical records, and presence of active cGVHD in the preceding 12 months was self-reported. The incidence of cGVHD in participants was 54%, of whom 46% reported active cGVHD. In multivariable analyses, subjects with active cGVHD were more likely to report adverse general health, mental health, functional impairments, activity limitation, and pain than were those with no history of cGVHD. However, health status did not differ between those with resolved cGVHD and those who never had cGVHD. We conclude that active cGVHD has a significant impact on many aspects of the overall health status of HCT survivors and that, most importantly, those successfully treated for cGVHD do not appear to have long-term impairments.
Multiple vitamin K-dependent coagulation zymogens promote adenovirus-mediated gene delivery to hepatocytes
Authors: Parker Alan L. , Waddington Simon N. , Nicol Campbell G. , Shayakhmetov Dmitry M. , Buckley Suzanne M. , Denby Laura , Kemball-Cook Geoffrey , Ni Shaoheng , Lieber Andre , McVey John H. , Nicklin Stuart A. , Baker Andrew H.
Published: June 2006

Upon local delivery, adenovirus (Ad) serotype 5 viruses use the coxsackie and Ad receptor (CAR) for cell binding and αv integrins for internalization. When administered systemically, however, their role in liver tropism is limited because CAR-permissive and mutated viruses show similar biodistribution, a finding recently attributed to blood coagulation factor (F) IX or complement protein C4BP binding to the adenovirus fiber and “bridging” to either low-density lipoprotein receptor-related protein or heparan sulfate proteoglycans. Here, we show that hepatocyte transduction in vitro can be enhanced by the vitamin K-dependent factors FX, protein C, and FVII in addition to FIX but not by prothrombin (FII), FXI, and FXII. This phenomenon was not dependent on proteolytic activation or cell signaling activity and for FX was mediated by direct virus-factor binding. Human FX substantially enhanced hepatocyte transduction by CAR-permissive and mutated viruses in an ex vivo liver perfusion model. In vivo, global down-regulation of vitamin K-dependent zymogens by warfarin significantly diminished liver uptake of CAR-deleted Ads; however, this phenomenon was fully rescued by acute infusion of human FX. Our results indicate a common and pivotal role for distinct vitamin K-dependent coagulation factors in mediating hepatocyte transduction by adenoviruses in vitro and in vivo.
The features of Drosophila core promoters revealed by statistical analysis
Authors: Gershenzon Naum I , Trifonov Edward N , Ioshikhes Ilya P
Published: June 2006

Background

Experimental investigation of transcription is still a very labor- and time-consuming process. Only a few transcription initiation scenarios have been studied in detail. The mechanism of interaction between basal machinery and promoter, in particular core promoter elements, is not known for the majority of identified promoters. In this study, we reveal various transcription initiation mechanisms by statistical analysis of 3393 nonredundant Drosophila promoters.

Results

Using Drosophila-specific position-weight matrices, we identified promoters containing TATA box, Initiator, Downstream Promoter Element (DPE), and Motif Ten Element (MTE), as well as core elements discovered in Human (TFIIB Recognition Element (BRE) and Downstream Core Element (DCE)). Promoters utilizing known synergetic combinations of two core elements (TATA_Inr, Inr_MTE, Inr_DPE, and DPE_MTE) were identified. We also establish the existence of promoters with potentially novel synergetic combinations: TATA_DPE and TATA_MTE. Our analysis revealed several motifs with the features of promoter elements, including possible novel core promoter element(s). Comparison of Human and Drosophila showed consistent percentages of promoters with TATA, Inr, DPE, and synergetic combinations thereof, as well as most of the same functional and mutual positions of the core elements. No statistical evidence of MTE utilization in Human was found. Distinct nucleosome positioning in particular promoter classes was revealed.

Conclusion

We present lists of promoters that potentially utilize the aforementioned elements/combinations. The number of these promoters is two orders of magnitude larger than the number of promoters in which transcription initiation was experimentally studied. The sequences are ready to be experimentally tested or used for further statistical analysis. The developed approach may be utilized for other species.
Effects of work-related factors on the breastfeeding behavior of working mothers in a Taiwanese semiconductor manufacturer: a cross-sectional survey
Authors: Chen Yi Chun , Wu Ya-Chi , Chie Wei-Chu
Published: June 2006

Background

In recent years, the creation of supportive environments for encouraging mothers to breastfeed their children has emerged as a key health issue for women and children. The provision of lactation rooms and breast pumping breaks have helped mothers to continue breastfeeding after returning to work, but their effectiveness is uncertain. The aim of this study was to assess the effects of worksite breastfeeding-friendly policies and work-related factors on the behaviour of working mothers.

Methods

This study was conducted at a large Taiwanese semiconductor manufacturer in August-September 2003. Questionnaires were used to collect data on female employees' breastfeeding behaviour, child rearing and work status when raising their most recently born child. A total of 998 valid questionnaires were collected, giving a response rate of 75.3%.

Results

The results showed that 66.9% of survey respondents breastfed initially during their maternity leave, which averaged 56 days. Despite the provision of lactation rooms and breast pumping breaks, only 10.6% mothers continued to breastfeed after returning to work, primarily office workers and those who were aware of their company's breastfeeding-friendly policies.

Conclusion

In conclusion, breastfeeding-friendly policies can significantly affect breastfeeding behaviour. However, an unfavourable working environment, especially for fab workers, can make it difficult to implement breastfeeding measures. With health professionals emphasizing that the importance of breastfeeding for infant health, and as only females can perform lactation, it is vital that women's work "productive role" and family "reproductive role" be respected and accommodated by society.
PCR-based generation of shRNA libraries from cDNAs
Authors: Du Cheng , Ge Baosheng , Liu Zhongfeng , Fu Kai , Chan Wing C , McKeithan Timothy W
Published: June 2006

Background

The use of small interfering RNAs (siRNAs) to silence target gene expression has greatly facilitated mammalian genetic analysis by generating loss-of-function mutants. In recent years, high-throughput, genome-wide screening of siRNA libraries has emerged as a viable approach. Two different methods have been used to generate short hairpin RNA (shRNA) libraries; one is to use chemically synthesized oligonucleotides, and the other is to convert complementary DNAs (cDNAs) into shRNA cassettes enzymatically. The high cost of chemical synthesis and the low efficiency of the enzymatic approach have hampered the widespread use of screening with shRNA libraries.

Results

We report here an improved method for constructing genome-wide shRNA libraries enzymatically. The method includes steps of cDNA fragmentation and endonuclease MmeI digestion to generate 19-bp fragments, capping the 19-bp cDNA fragments with a hairpin oligonucleotide, and amplification of the hairpin structures by PCR. The PCR step converts hairpins into double-stranded DNAs that contain head-to-head cDNA fragments that can be cloned into a vector downstream of a Pol III promoter.

Conclusion

This method can readily be used to generate shRNA libraries from a small amount of mRNA and thus can be used to create cell- or tissue-specific libraries.
An ELISA-based procedure for assaying proteins in digests of human leukocytes and cell lines, using specifically selected peptides and appropriate antibodies
Authors: Braitbard Ori , Bishara-Shieban Janette , Glickstein Hava , Kott-Gutkowski Miriam , Pace Umberto , Rund Deborah G , Stein Wilfred D
Published: June 2006

Background

We describe the application of an ELISA-based assay (the Peptidomatrix) that can be used to simultaneously identify and quantitate a number of proteins in biological samples. The biological sample (blood component, biopsy, culture or other) is first lysed to release all the proteins, without any additional separation. The denatured proteins in the sample are then digested in bulk with the desired proteolytic enzyme(s). The peptides in the digest are then assayed by appropriate antibodies, using a competition ELISA protocol.

Results

As an example of its use, the present paper applies the Peptidomatrix to the assay of four membrane proteins MDR1 (P-glycoprotein or ABCB1), MRP1 (ABCC1), BCRP/MXR (ABCG2) and the alpha subunit of the Na, K_ATPase (ATP1A1), present in a number of cell lines and in human lymphocytes. We show that we can detect and quantitate these proteins, using a series of peptide-antibody pairs, and that we can differentiate between cell lines or cell preparations that express the target proteins and those that do not.

Conclusion

We have devised a simple, ELISA-based proteomics assay that enables the quantitation of designated proteins in a cell or tissue sample, and that can be used in any laboratory, with minimal specialized equipment.
Recent developments in biofeedback for neuromotor rehabilitation
Authors: Huang He , Wolf Steven L , He Jiping
Published: June 2006

The original use of biofeedback to train single muscle activity in static positions or movement unrelated to function did not correlate well to motor function improvements in patients with central nervous system injuries. The concept of task-oriented repetitive training suggests that biofeedback therapy should be delivered during functionally related dynamic movement to optimize motor function improvement. Current, advanced technologies facilitate the design of novel biofeedback systems that possess diverse parameters, advanced cue display, and sophisticated control systems for use in task-oriented biofeedback. In light of these advancements, this article: (1) reviews early biofeedback studies and their conclusions; (2) presents recent developments in biofeedback technologies and their applications to task-oriented biofeedback interventions; and (3) discusses considerations regarding the therapeutic system design and the clinical application of task-oriented biofeedback therapy. This review should provide a framework to further broaden the application of task-oriented biofeedback therapy in neuromotor rehabilitation.
Glucagon Suppression of Ghrelin Secretion Is Exerted at Hypothalamus-Pituitary Level
Authors: Arafat A. M. , Perschel F. H. , Otto B. , Weickert M. O. , Rochlitz H. , Schöfl C. , Spranger J. , Möhlig M. , Pfeiffer A. F. H.
Published: June 2006

Context: The mechanisms underlying the well-known glucagon-induced satiety effect are unclear. Recently, we showed that glucagon induces a remarkable decrease in the orexigenic hormone ghrelin that might be responsible for this effect.

Objective: The objective of this study was to evaluate the putative role of the hypothalamic pituitary axis in glucagon’s suppressive effect on ghrelin secretion.

Design, Subjects, and Methods: Prospectively, we studied the endocrine and metabolic responses to im glucagon administration in 22 patients (16 males; age, 21–68 yr; body mass index, 28.1 ± 1.1 kg/m2) with a known hypothalamic-pituitary lesion and at least one pituitary hormone deficiency. Control experiments were performed in 27 healthy subjects (15 males; age, 19–65 yr; body mass index, 25.5 ± 0.9 kg/m2).

Results: The suppression of ghrelin by glucagon measured as area under the curve240min was significantly greater in controls when compared with patients (P < 0.01). Although there was a significant decrease in ghrelin in controls (P < 0.001), ghrelin was almost unchanged in patients (P = 0.359). Changes in glucagon, glucose, and insulin levels were comparable between both groups.

Conclusions: We show that the hypothalamic-pituitary axis plays an essential role in the suppression of ghrelin induced by im glucagon administration. Glucagon significantly decreases ghrelin levels in healthy subjects. However, in the absence of an intact hypothalamic-pituitary axis, this effect was abolished. The mechanisms responsible for our observation are unlikely to include changes in glucose or insulin levels.
Associations of Adiposity from Childhood into Adulthood with Insulin Resistance and the Insulin-Like Growth Factor System: 65-Year Follow-Up of the Boyd Orr Cohort
Authors: Martin Richard M. , Holly Jeff M. P. , Davey Smith George , Gunnell David
Published: June 2006

Context: One metabolic pathway through which adiposity influences disease risk may be via alterations in insulin and IGF metabolism.

Objective: Our objective was to investigate associations of adiposity at different stages of life with insulin and the IGF system.

Design, Setting, and Participants: The study was a 65-yr follow-up of 728 Boyd Orr cohort participants (mean age, 71 yr) originally surveyed between 1937 and 1939.

Main Outcomes: Outcomes included homeostasis model assessment of insulin resistance, total IGF-I and IGF-II, IGF binding protein (IGFBP)-2, and IGFBP-3 in adulthood.

Results: Childhood body mass index (BMI) was weakly inversely related to adult IGF-I (coefficient per BMI sd, −3.4 ng/ml; 95% confidence interval, −7.3 to 0.5; P = 0.09). IGF-II (but not IGF-I) increased with higher current fat mass index (coefficient, 26.1 ng/ml; 95% confidence interval, 4.6 to 47.6; P = 0.02) and waist-hip ratio (30.0 ng/ml; 9.4 to 50.5; P = 0.004). IGFBP-2 decreased by 21.2% (17.2 to 24.9; P < 0.001), and homeostasis model assessment of insulin resistance increased by 38.8% (28.9 to 49.6; P < 0.001) per sd higher adult BMI. Among thin adults (BMI tertiles 1 and 2), IGFBP-2 was positively, and insulin resistance was inversely, associated with childhood BMI.

Conclusion: There was only weak evidence that associations of childhood BMI with chronic disease risk may be mediated by adult IGF-I levels. Circulating IGFBP-2 in adulthood, a marker for insulin sensitivity, was inversely associated with current adiposity, but overweight children who became relatively lean adults were more insulin sensitive than thinner children. The findings may indicate programming of later insulin sensitivity and consequently IGFBP-2 levels in response to childhood adiposity. The role of IGF-II in obesity-related chronic diseases warrants additional investigation.
Ablation of the single dynamin of T. brucei blocks mitochondrial fission and endocytosis and leads to a precise cytokinesis arrest
Authors: Chanez Anne-Laure , Hehl Adrian B. , Engstler Markus , Schneider André
Published: June 2006

Mitochondrial fission is mediated by dynamin-like proteins (DLPs). Trypanosoma brucei contains a single DLP, which is the only member of the dynamin superfamily. We have previously shown that expression of the human proapoptotic Bax in T. brucei induces extensive mitochondrial fragmentation. Here we report that Baxinduced mitochondrial fission is abolished in cell lines lacking functional DLP suggesting that the protein is also required for mitochondrial division during the cell cycle. Furthermore, DLP-ablated cells are deficient for endocytosis and as a consequence accumulate enlarged flagellar pockets. Thus, besides its expected role in mitochondrial fission the trypanosomal DLP is required for endocytosis, a function thought to be restricted to classical dynamins. In agreement with its dual function, the DLP localizes to both the mitochondrion and the flagellar pocket, the site where endocytosis occurs. Unexpectedly, ablation of DLP also causes an arrest of cytokinesis. The fact that no multinucleation is observed in the arrested cells argues for a precise cell-cycle block. Furthermore, analysis of a clathrin-knockdown cell line suggests that the cytokinesis arrest is not due to the endocytosis defect. Thus, our results support a working model in which mitochondrial fission triggers a checkpoint for cytokinesis.
Tomosyn-1 is involved in a post-docking event required for pancreatic β-cell exocytosis
Authors: Cheviet Séverine , Bezzi Paola , Ivarsson Rosita , Renström Erik , Viertl David , Kasas Sandor , Catsicas Stefan , Regazzi Romano
Published: June 2006

Although the assembly of a ternary complex between the SNARE proteins syntaxin-1, SNAP25 and VAMP2 is known to be crucial for insulin exocytosis, the mechanisms controlling this key event are poorly understood. We found that pancreatic β-cells express different isoforms of tomosyn-1, a syntaxin-1-binding protein possessing a SNARE-like motif. Using atomic force microscopy we show that the SNARE-like domain of tomosyn-1 can form a complex with syntaxin-1 and SNAP25 but displays binding forces that are weaker than those observed for VAMP2 (237±13 versus 279±3 pN). In pancreatic β-cells tomosyn-1 was found to be concentrated in cellular compartments enriched in insulin-containing secretory granules. Silencing of tomosyn-1 in the rat β-cell line INS-1E by RNA interference did not affect the number of secretory granules docked at the plasma membrane but led to a reduction in stimulus-induced exocytosis. Replacement of endogenous tomosyn-1 with mouse tomosyn-1, which differs in the nucleotide sequence from its rat homologue and escapes silencing, restored a normal secretory rate. Taken together, our data suggest that tomosyn-1 is involved in a post-docking event that prepares secretory granules for fusion and is necessary to sustain exocytosis of pancreatic β-cells in response to insulin secretagogues.
Synthesis and Properties of Naphthopyrans with a Benzothiophene Ring
Authors: Uchida Manabu , Kume Makoto , Irie Masahiro
Published: June 2006

New photochromic benzochromene derivatives condensed with a benzothiophene ring were synthesized. The condensation positions of the thiophene ring influenced the photochromism. 7a-Methyl-7aH-benzo[f][1]benzothieno[2,3-b]chromene (1) underwent a two-photon two-step photochromism, while 7a-methyl-7aH-benzo[f][1]benzothieno[3,2-b]chromene (2) showed an ordinary chromene-type photochromic reaction. The yellow color of 1 disappeared upon irradiation with 405 nm light, and a thermally stable oxabicyclo[3.1.0]hexene isomer was reversibly produced. On the other hand, compound 2 turned orange upon irradiation with 366 nm light, and the orange color quickly returned to the original pale yellow in the dark. Upon irradiation with both 366 and >420 nm light compound 2 isomerized to an oxabicyclo[3.1.0]hexene form.
A Pummerer-Type Novel Ring Fission of 2-Methylsulfinyl-5,6-dihydro-4H-1,3,4-thiadiazine Derivatives: A Homologation of Aldehydes and Ketones
Authors: Shimada Kazuaki , Otaki Akihiro , Yanakawa Masaki , Mabuchi Shosuke , Yamakado Naoya , Shimoguchi Takeshi , Inoue Kazuya , Kagawa Takashi , Shoji Kazutoshi , Takikawa Yuji
Published: June 2006

Aldehydes and ketones were converted into 2-methylsulfinyl-5,6-dihydro-4H-1,3,4-thiadiazines via the formation and base-induced ring-closure of N-alkylidene-N′-bis(alkylthio)methylenehydrazines followed by mCPBA oxidation. The subsequent Pummerer-type ring fission of the rings was performed by treating with trifluoroacetic anhydride or trifluoromethanesulfonic anhydride at −78 °C to give α,β-unsaturated esters and ketones in modest yields. Thus, this reaction sequence was regarded as being a new method for the two-carbon homologation of aldehydes and ketones.
Lipase-Catalyzed Transesterification of Aryl-Substituted Alkanols in an Organic Solvent
Authors: Nakamura Kaoru , Kawasaki Masashi , Ohno Atsuyoshi
Published: June 2006

Lipase-catalyzed transesterifications of aryl-substituted alcohols with vinyl acetate in organic solvents have been investigated. Vmax of (R)-1-phenylethanol is much larger than its (S)-counterpart, although their Kms are similar each other. It is proposed that a lipase from Pseudomonas cepacia can form a complex easily with each enantiomer, although the complex with the (S)-enantiomer is abortive. Enantioselectivity for the ortho-substituted 1-phenylethanol is smaller than those for the others. A three-dimensional model for the active domain of the lipase has been proposed to explain the enantioselectivity and substrate selectivity of the lipase.
Thermal Dimerization of Alkali Acrylate/3-Methyl-3-butenoate and Alkali Methacrylate/3-Methyl-3-butenoate Binary Systems in the Solid State
Authors: Akutsu Fumihiko , Inoki Mari , Nishimura Nozomu , Kasashima Yoshio , Naruchi Kiyoshi
Published: June 2006

The thermal reaction in the solid state of binary salts, obtained from an equimolar mixture solution, of lithium 3-methyl-3-butenoate/methacrylate (3-MBA/MA) or potassium 3-MBA/MA, after esterification, produced mainly dimethyl (Z)-3,6-dimethyl-2-heptenedioate as a novel cross-coupled dimer. The cross-coupled dimer was obtained from the potassium salts in 35.5% yield upon heating at 230 °C for 2 h. Similary, a methyl ester of the cross-coupled dimer, dimethyl (Z)-3-methyl-2-heptenedioate, was given from sodium 3-methyl-3-butenoate/acrylate (3-MBA/AA) or potassium 3-MBA/AA after esterification. The cross-coupled dimer was obtained from potassium 3-MBA/AA in 57.5% yield upon heating at 230 °C for 2 h. The X-ray diffraction pattern of potassium 3-MBA/MA or potassium 3-MBA/AA indicates the formation of a new phase, that is different from that of the individual salts. The crystal system of K–(3-MBA/AA) was transformed to a more stable state by initial heating for 20 min. The selective cross-coupled dimerization was caused by the new phase of binary salts and maintaining the crystal state of the reaction system by the formation of solid-solution crystals.
Preference of Electron Transfer to Nucleophilic Addition in Reactions of Ketene Silyl Acetals with Quinones and Catalysis of Magnesium Ion
Authors: Fujita Morifumi , Fukuzumi Shunichi , Matsubayashi Gen-etsu , Otera Junzo
Published: June 2006

β,β-Dimethyl-substituted ketene silyl acetal (1a) reduces p-chloranil and other activated quinones with electron-withdrawing substituents to produce the carbon–oxygen adduct, the hydrolysis of which yields the corresponding hydroquinone ether. The structure of the hydroquinone ether has been determined by the X-ray crystal analysis. The reactions are significantly slowed down in benzene where the charge-transfer spectra of electron donor–acceptor complexes formed between 1a and the activated quinones are observed. The comparison of the observed rate constant with that predicted for the electron transfer process from 1a to p-chloranil indicates that the addition of 1a to p-chloranil proceeds via the electron transfer from 1a to p-chloranil. Although no reaction takes place between 1a and p-benzoquinone, the electron affinity of which is significantly smaller than that of p-chloranil, the reduction of p-benzoquinone by 1a occurs efficiently in the presence of magnesium ion. The kinetic expression of the Mg2+ catalysis changes from the first-order to second-order in [Mg2+] under the conditions that Mg2+ forms the 2 : 1 complexes with the corresponding radical anions. The catalytic effects of Mg2+ are approximately the same as those observed for the electron transfer reduction of these oxidants, demonstrating the important contribution of the Mg2+-catalyzed electron transfer process in the addition of 1a to p-benzoquinone. On the other hand, the reaction of a nonsubstituted ketene silyl acetal (1d) with p-fluoranil yields the carbon–carbon adduct rather than the carbon–oxygen adduct. The much larger rate constants of 1d than those of 1a despite the higher oxidation potential of 1d suggest that the 1,2-addition to p-fluoranil occurs via the nucleophilic attack of 1d, which is much less sterically hindered than 1a, to the positively charged carbonyl carbon of p-fluoranil rather than an alternative electron transfer pathway.