bluuebunny/crossref_metadata_2025 huggingface dataset:
Retrospective Analysis of Coagulation Factor II Receptor (F2R) Sequence Variation and Coronary Heart Disease in Hypertensive Patients
Authors: Gigante Bruna , Bellis Alessandro , Visconti Roberta , Marino Marina , Morisco Carmine , Trimarco Valentina , Galasso Gennaro , Piscione Federico , De Luca Nicola , Prince Jonathan A. , de Faire Ulf , Trimarco Bruno
Published: March 2007

Objectives—The purpose of this study was to evaluate the role of genetic variants within the coagulation factor II receptor (F2R) in the occurrence of coronary heart disease (CHD).

Methods and Results—Four SNPs (−1738 G/A, 2860 G/A, 2930 T/C, and 9113 C/A) and an ins/del polymorphism −506-/GGCCGCGGGAAGC (D/I), replicating a consensus sequence for Ets-1 transcription factor, and their related haplotypes were tested for association to CHD in 1600 hypertensive patients divided in 2 groups according to presence (cases, n=559) and absence (controls, n=1041) of CHD. Allele I at −506 locus was associated with increased risk of CHD under additive, dominant, and recessive models of inheritance (allP<0.01). Three haplotypes carrying I allele were consistently associated with an increased risk of CHD (allP<0.05). Patients homozygous for the C allele at the 2930 locus also showed an increased risk of CHD (P<0.05). To test the functionality of −506 locus, nuclear extracts were incubated with −506D and −506I sequences by EMSA and F2R promoter activity (F2R-A) were assessed in HUVECs transfected with vectors carrying −506D and −506I sequences and exposed to hypoxia. Presence of the −506I sequence was associated with a 26% reduction of affinity binding to nuclear proteins and to blunted F2R-A in response to hypoxia as compared with the −506D sequence (allP<0.05).

Conclusions—F2R genetic variants may influence the natural history of CHD in patients at high risk of cardiovascular events.
A Maximum-Likelihood Interpretation for Slow Feature Analysis
Authors: Turner Richard , Sahani Maneesh
Published: March 2007

The brain extracts useful features from a maelstrom of sensory information, and a fundamental goal of theoretical neuroscience is to work out how it does so. One proposed feature extraction strategy is motivated by the observation that the meaning of sensory data, such as the identity of a moving visual object, is often more persistent than the activation of any single sensory receptor. This notion is embodied in the slow feature analysis (SFA) algorithm, which uses “slowness” as a heuristic by which to extract semantic information from multidimensional time series. Here, we develop a probabilistic interpretation of this algorithm, showing that inference and learning in the limiting case of a suitable probabilistic model yield exactly the results of SFA. Similar equivalences have proved useful in interpreting and extending comparable algorithms such as independent component analysis. For SFA, we use the equivalent probabilistic model as a conceptual springboard with which to motivate several novel extensions to the algorithm.
State-Space Models: From the EM Algorithm to a Gradient Approach
Authors: Olsson Rasmus Kongsgaard , Petersen Kaare Brandt , Lehn-Schiøler Tue
Published: March 2007

Slow convergence is observed in the EM algorithm for linear state-space models. We propose to circumvent the problem by applying any off-the-shelf quasi-Newton-type optimizer, which operates on the gradient of the log-likelihood function. Such an algorithm is a practical alternative due to the fact that the exact gradient of the log-likelihood function can be computed by recycling components of the expectation-maximization (EM) algorithm. We demonstrate the efficiency of the proposed method in three relevant instances of the linear state-space model. In high signal-to-noise ratios, where EM is particularly prone to converge slowly, we show that gradient-based learning results in a sizable reduction of computation time.
Variational Bayes Solution of Linear Neural Networks and Its Generalization Performance
Authors: Nakajima Shinichi , Watanabe Sumio
Published: March 2007

It is well known that in unidentifiable models, the Bayes estimation provides much better generalization performance than the maximum likelihood (ML) estimation. However, its accurate approximation by Markov chain Monte Carlo methods requires huge computational costs. As an alternative, a tractable approximation method, called the variational Bayes (VB) approach, has recently been proposed and has been attracting attention. Its advantage over the expectation maximization (EM) algorithm, often used for realizing the ML estimation, has been experimentally shown in many applications; nevertheless, it has not yet been theoretically shown. In this letter, through analysis of the simplest unidentifiable models, we theoretically show some properties of the VB approach. We first prove that in three-layer linear neural networks, the VB approach is asymptotically equivalent to a positive-part James-Stein type shrinkage estimation. Then we theoretically clarify its free energy, generalization error, and training error. Comparing them with those of the ML estimation and the Bayes estimation, we discuss the advantage of the VB approach. We also show that unlike in the Bayes estimation, the free energy and the generalization error are less simply related with each other and that in typical cases, the VB free energy well approximates the Bayes one, while the VB generalization error significantly differs from the Bayes one.
Synergies Between Intrinsic and Synaptic Plasticity Mechanisms
Authors: Triesch Jochen
Published: March 2007

We propose a model of intrinsic plasticity for a continuous activation model neuron based on information theory. We then show how intrinsic and synaptic plasticity mechanisms interact and allow the neuron to discover heavy-tailed directions in the input. We also demonstrate that intrinsic plasticity may be an alternative explanation for the sliding threshold postulated in the BCM theory of synaptic plasticity. We present a theoretical analysis of the interaction of intrinsic plasticity with different Hebbian learning rules for the case of clustered inputs. Finally, we perform experiments on the “bars” problem, a popular nonlinear independent component analysis problem.
Distinguishing Causal Interactions in Neural Populations
Authors: Seth Anil K. , Edelman Gerald M.
Published: March 2007

We describe a theoretical network analysis that can distinguish statistically causal interactions in population neural activity leading to a specific output. We introduce the concept of a causal core to refer to the set of neuronal interactions that are causally significant for the output, as assessed by Granger causality. Because our approach requires extensive knowledge of neuronal connectivity and dynamics, an illustrative example is provided by analysis of Darwin X, a brain-based device that allows precise recording of the activity of neuronal units during behavior. In Darwin X, a simulated neuronal model of the hippocampus and surrounding cortical areas supports learning of a spatial navigation task in a real environment. Analysis of Darwin X reveals that large repertoires of neuronal interactions contain comparatively small causal cores and that these causal cores become smaller during learning, a finding that may reflect the selection of specific causal pathways from diverse neuronal repertoires.
Independent Slow Feature Analysis and Nonlinear Blind Source Separation
Authors: Blaschke Tobias , Zito Tiziano , Wiskott Laurenz
Published: March 2007

In the linear case, statistical independence is a sufficient criterion for performing blind source separation. In the nonlinear case, however, it leaves an ambiguity in the solutions that has to be resolved by additional criteria. Here we argue that temporal slowness complements statistical independence well and that a combination of the two leads to unique solutions of the nonlinear blind source separation problem. The algorithm we present is a combination of second-order independent component analysis and slow feature analysis and is referred to as independent slow feature analysis. Its performance is demonstrated on nonlinearly mixed music data. We conclude that slowness is indeed a useful complement to statistical independence but that time-delayed second-order moments are only a weak measure of statistical independence.
Praxis of Empowerment
Authors: Issa Daniela
Published: March 2007

The mística of Brazil’s Landless Rural Workers’ Movement developed from Latin American liberation theology and is generally interpreted as love for a cause, solidarity experienced in collectivity, and belief in change. Not only an emotional element, however, it is a praxis of pedagogy and culture developed by the movement to construct its collective identity and preserve its cultural roots against the homogenization of globalization. Art and symbolism are used in practices that not only educate but empower by example and reflect the collective memory of the Landless. The movement incorporates these practices into its struggles, keeping the inspiration alive without institutionalizing the mística.
Neo-Zapatista Network Politics
Authors: Swords Alicia C. S.
Published: March 2007

As Zapatista support-base communities consolidate their autonomy, a variety of organizations have taken up lessons from the Zapatistas. Neo-Zapatista organizations—grassroots and nongovernmental organizations that support the Zapatistas’ demands—are developing alternative practices of participatory democracy and autonomous development. These practices include “rule by obeying,” resisting government programs, strengthening cooperatives, diversifying production, and building food security. By implementing these practices, neoZapatista networks transform hegemonic meanings and practices of procedural democracy and neoliberal development by reembedding economic and political decision making in social values. A case study of three such organizations documents the learning processes by which they generate constructive meanings and practices that reconfigure social power.
Resisting Neoliberal Homogenization
Authors: Stahler-Sholk Richard
Published: March 2007

The Zapatista autonomy movement in Chiapas, Mexico, is a significant example of rising social-movement resistance to neoliberalism. The neoliberal project in Latin America since the 1980s has led to a retrenchment of the state, opening new space for social movements to contest power from below. In Mexico, the weakening of corporatist and clientelist mechanisms once controlled by the party-state allowed groups like the Zapatistas to assert rights based on both collective (ethnic) identity and Mexican national citizenship. An examination of the Zapatista autonomy movement since 1994 suggests several dilemmas: (1) A territorially based model of autonomy as administrative decentralization would not fundamentally alter existing political hierarchies or the role of the state as broker for global capital. (2) Autonomy conceived as mere disengagement would leave autonomous communities cut off from resources and unprotected from the forces of the global market. (3) Autonomy defined as simply cultural pluralism falls into the neoliberal “multiculturalism trap” of atomizing communities, substituting formal “equality” for the power to establish collective identities and demand substantive rights. The Zapatistas have maneuvered around counterinsurgency and co-optation through a flexible, community-based model of autonomy, shifting in 2003 to a model of regional Juntas de Buen Gobierno with rotating representatives to integrate the resistance. The experiment holds lessons for other social movements in Latin America struggling to preserve grassroots decision making in opposition to the logic of global capital.
Struggles against Accumulation by Dispossession in Bolivia
Authors: Spronk Susan , Webber Jeffery R.
Published: March 2007

David Harvey suggests that, compared with struggles waged by traditional political parties and labor unions, struggles to “reclaim the commons” typically result in a less focused political dynamic of social action, which is both a strength and a weakness. While these social movements draw strength from their embeddedness in daily life, not all manage to make the link between the struggle against accumulation by dispossession and the struggle for expanded reproduction that is necessary to meet the material needs of impoverished and repressed populations. Social movements in Bolivia have framed their demands differently in the struggles against the privatization of natural gas and water depending on the different roles these resources play in the region’s political economy. Struggles against the privatization of natural gas pose a greater challenge to neoliberalism because of their macro frame and politics.
Neoliberalism, Corruption, and Legacies of Contention
Authors: Villalón Roberta
Published: March 2007

Beginning in 1993, an innovative grassroots wave of social and political contention spread throughout Argentina. A heterogeneous mass of unemployed and otherwise disadvantaged citizens created alternative means of dissent and organizations that displaced traditional institutions such as unions and political parties as the main channels of societal representation. The development of this wave of contention was related to the negative consequences of neoliberal reforms, embedded in a long-standing crisis of institutional legitimacy, and inspired by a rich legacy of social and political activism. The institutionalization of the movement contributed to its growth and longevity but lessened its radical character and its potential to become a competitive governing force.
Risk of Incarceration among Male Veterans and Nonveterans
Authors: Greenberg Greg A. , Rosenheck Robert A. , Desai Rani A.
Published: March 2007

In this study, we used data from national surveys of U.S. veterans and nonveterans to investigate whether military service increased risk for incarceration compared to non-veteran peers. White veterans aged thirty-five to fifty-four (early years of the All Volunteer Force and the Vietnam era) were at higher risk for incarceration than white nonveterans. Black and Hispanic veterans of these eras were generally at lower risk of incarceration than age-and race-matched nonveterans. For all racial/ethnic groups, the risk of incarceration among veterans compared to nonveterans declined among those who served in the later years of the implementation of the All Volunteer Force. These findings may reflect the disadvantaged backgrounds of recruits during the early implementation of the All Volunteer Force, from 1973 to 1980, and the improved quality of personnel recruited after 1980. Among all males, the risk of incarceration was not elevated among Vietnam-era and World War II veterans.
A Review of the Literature on Veterans Published in Armed Forces & Society, 1974-2006
Authors: Camacho Paul R. , Atwood Paul L.
Published: March 2007

The article presented here is a review of the twenty-four articles, research notes, or book reviews pertaining to veterans that have appeared in our journal since its inception in 1974. For the purposes of discussion, the articles are divided into a thematic scheme. Following each thematic section, the authors pose a number of potential research projects that, in their opinion, would advance research on veterans' issues and may be of interest to our members.
A Sociological View of the Vietnam Veterans' Lobby
Authors: Camacho Paul R. , Sutton Paul
Published: March 2007

A synopsis of the state of affairs of the Vietnam veterans lobby illustrates that veterans' interest-group activity is filled with conflict. First, we acknowledge the efforts of the veterans' community before Vietnam. Second, we summarize the activism that developed during the Vietnam decade, noting the conflict between the World War II/Korea veterans and the Vietnam “Homecomers.”1 That clash provided the rationale for two bureaucratic “wars” over control of veterans' policy, programs, budgets, and the client base of Vietnam and Vietnam-era veterans: one involving the (then) Veterans Administration (VA) and Health, Education, and Welfare over veterans' educational programs, the other involving the VA and Department of Labor over veteran outreach centers. We summarize two salient issues: Agent Orange and small-business opportunities. Finally, we illustrate that the difficulties confronted by the Vietnam generation also confront the Gulf War/Afghanistan and Iraq veterans. We conclude with comments about the possible future of the veterans as an interest group and the Department of Veterans Affairs.
Communication Policy Changes in State Adult Correctional Facilities From 1971 to 2005
Authors: Hoffmann Heath C. , Dickinson George E. , Dunn Chelsea L.
Published: March 2007

The objective of this research is to document correctional institutions’ policies regarding inmates’ correspondence, visitation, and telephoning between 1971 and 2005. Data were gathered via mailed surveys in 1971, 1981, 1991, and 2005 from state correctional facilities for adults in maximum security institutions. The survey return rates were 93% ( n = 64) in 1971, 96% ( n = 66) in 1981, 81% ( n = 91) in 1991, and 84% ( n = 162) in 2005. The findings suggest that prison communication policies are becoming more restrictive on visitation and inmates are assuming more of the expenses for correspondence. At the same time, policies regarding telephone usage seem to have gotten more lenient, with the financial obligations falling solely on the inmates. These results are informative as many state legislatures are becoming increasingly attentive to strategies that might reinforce inmate relationships with family and friends to reduce recidivism rates, lessening the financial strain of incarceration on state budgets.
Measuring Interdisciplinary Perceptions of Collaboration on Hospice Teams
Authors: Oliver Debra Parker , Wittenberg-Lyles Elaine M. , Day Michele
Published: March 2007

This project modified the Index for Interdisciplinary Collaboration to create a tool that could measure perceptions of collaboration by all members of the hospice team. Questions on the 42-item instrument were reworded to be more inclusive. This new Modified Index for Interdisciplinary Collaboration (MIIC) showed strong reliability for the total instrument and the original instrument subscales. Further use and testing of this instrument is recommended.
AIDS and Palliative Care in South Africa
Authors: Demmer Craig
Published: March 2007

As a result of limited access to antiretroviral treatment, many South Africans die yearly of AIDS. It is important that the end-of-life needs of these people be met. This article examines the major challenges involved in providing quality end-of-life care to people with AIDS in South Africa. Published reports are reviewed, as is the author's experience living and working in KwaZulu-Natal, South Africa. The issues discussed include the nature of the South African health care system, with emphasis on the scarcity of palliative care resources for AIDS patients, ineffective control of pain, models of care such as the integrated community-based home care model that relies heavily on community caregivers to meet the needs of people dying of AIDS, the living conditions of AIDS patients and their families, and AIDS-related stigma. Broad recommendations are presented for improving palliative care services for people with AIDS in the South African context.
Defaulting Oncology Patient in a Multispecialty State-Run Hospital in India
Authors: Gupta Deepak , Bhatnagar Sushma , Mishra Seema
Published: March 2007

A 14-year-old boy diagnosed with primitive neuroectodermal tumor of the L5 vertebra defaulted from his treatment, which significantly contributed to the progression of his disease. The possible causes of defaulting were (1) poor doctor/patient rapport, (2) inadequate communication between doctor and patient about the disease and its treatment, (3) unavailability of a “no show” defaulters' compliance program and case managers, (4) patients' economic constraints, (5) additional inconveniences because of referrals and consultations in a large multispecialty state-run hospital, and (6) patient's low education level and poor understanding of the disease and its treatment. Defaulting is multifactorial but can be contained. Good doctor/patient rapport, with emphasis on effective communication is important in improving compliance. Institutional administrative procedures should be more user-friendly. Medical institutions should consider having a “no show” defaulters' compliance program and case managers in those specialties where defaulting can adversely affect the clinical outcome.
Conceptualizing Alzheimer's Disease as a Terminal Medical Illness
Authors: Wolf-Klein Gisele , Pekmezaris Renee , Chin Lisa , Weiner Joseph
Published: March 2007

Alzheimer's disease is a common illness of the elderly population, with an estimated prevalence of 4.5 million people in the United States and 24.3 million worldwide. Despite current pharmaceutic advances in delaying disease progression, there is no cure. This article reviews the evidence for conceptualizing Alzheimer's disease as a terminal medical illness. Discussed are principles of palliative care as applied to the patient with Alzheimer's disease and the patient's family.
Preliminary Statistical Assessment of Intervention by a Palliative Care Team Working in a Japanese General Inpatient Unit
Authors: Iwase Satoru , Murakami Tadashi , Saito Yuichiro , Nakagawa Keiichi
Published: March 2007

The effectiveness of intervention by the palliative care team at the University of Tokyo Hospital was assessed using the Support Team Assessment Schedule. During the study, 316 consecutive patients with malignant tumor disease were referred to the palliative care team, which assessed 11 physical symptoms. Results were tested by paired t test to calculate 95% confidence intervals comparing the mean Support Team Assessment Schedule scores for each symptom from the first time to the last time after palliative care intervention. The study concluded that (1) intervention by a palliative care team in general inpatient units can effectively control pain, nausea, and vomiting in patients up until the terminal stage; (2) it is likely that cough is controllable in the terminal stage with intervention by a palliative care team; (3) mouth dryness, anorexia, constipation, diarrhea, fatigue, and ascites are difficult to alleviate in the long term even with palliative intervention.
Medical Condition Is Related to Treatment Preference in Cancer Patients: Implications for Quality Assessment
Authors: Rohrer James E. , Lim Seah H. , Bock Frank Andrew
Published: March 2007

Ongoing communication with cancer patients about their treatment preferences is important. A survey assessing treatment preferences was distributed to 100 cancer patients who were newly diagnosed, 100 in remission after therapy, and 60 who had failed therapy/ relapsed; 100 cancer caregivers, and 100 noncancer patients attending the cancer center for benign hematologic problems. Almost 59% of respondents preferred treatment even if the chance of cure was less than 10%. Among subjects who did not have cancer, less than 50% wanted treatment under these circumstances, whereas over 70% of cancer patients who had failed treatment or relapsed wanted treatment ( P = .0994). Multiple logistic regression analysis revealed that the adjusted odds of preferring aggressive treatment were less for those without cancer and those with newly diagnosed cancer than for respondents who had failed treatment or were in relapse. The preference for aggressive cancer treatment is related to medical condition.
Spiritual Needs of Persons With Advanced Cancer
Authors: Hampton Diane M. , Hollis Dana E. , Lloyd Dudley A. , Taylor James , McMillan Susan C.
Published: March 2007

Spiritual needs, spiritual distress, and spiritual well-being of patients with terminal illnesses can affect their quality of life. The spiritual needs of patients with advanced cancer have not been widely studied. This study assessed the spiritual needs of 90 patients with advanced cancer who were newly admitted to hospice home care. They completed a demographic data form and the Spiritual Needs Inventory shortly after hospice admission. Scores could range from a low of 17 to a high of 85; study scores were 23 to 83. Results showed great variability in spiritual needs. Being with family was the most frequently cited need (80%), and 50% cited prayer as frequently or always a need. The most frequently cited unmet need was attending religious services. Results suggest the importance of a focus on the spiritual more than the religious in providing care to patients at the end of life.
Effectiveness of CancerGuides®: A Study of an Integrative Cancer Care Training Program for Health Professionals
Authors: Staples Julie K. , Wilson Amy T. , Pierce Beverly , Gordon James S.
Published: March 2007

Purpose: To determine how CancerGuidesâ®, an integrative cancer care training program, would affect participants' perception of their professional skills, their mood, use of self care and mind-body modalities, and the acceptance of integrative cancer care at their institutions. Study Design: Qualitative and quantitative measures were used during the training program and at 6-month follow-up. A focus group met before and after the training, and individual interviews of focus group participants were done at follow-up. Methods: The week-long program consisted of lectures that provided information on integrating conventional and complementary therapies into individualized programs of cancer care. Small group sessions used mind-body techniques to allow participants to understand the dilemmas faced by cancer patients. A self-report survey was administered at the training program and at 6-month follow-up. The survey included questions on the personal and professional use of modalities and on participants' sense of how well they met the course objectives. Qualitative questions addressed self-care, changes in clinical practice, and the acceptance of integrative therapies by their institutions. The Profile of Mood States was administered before and after the training. Results: Six months after the training, there was a significant increase in the use and/or recommendation of complementary and alternative medicine modalities in clinical practice and a significant increase in the personal practice of these modalities. Participants' perceived level of skill for all of the course objectives was significantly increased following the training and was maintained at 6-month follow-up. There were significant reductions in the Anger-Hostility and Tension-Anxiety subscale scores of the Profile of Mood States questionnaire. In response to qualitative questions, participants reported positive changes in patient care and in their clinical practices at 6-month follow-up. The subset of participants in the focus group interviews reported similar improvements. Thirty-five percent of those responding at follow-up reported an increase in acceptance of integrative cancer therapies at their institutions, and 77% reported making positive changes in self-care. Conclusions: Cancer-Guides provided training that allowed participants to enhance personal self-care, to interact more effectively with their patients, and to develop programs of integrative cancer care.
Surviving Against All Odds: Analysis of 6 Case Studies of Patients With Cancer Who Followed the Gerson Therapy
Authors: Molassiotis A. , Peat P.
Published: March 2007

A considerable number of patients with cancer have used or are using the Gerson therapy, an alleged anticancer metabolic diet. However, there is almost no scientific support for this regimen. Hence, the present case review study of 6 patients with metastatic cancer who used the Gerson therapy aims at critically evaluating each case to derive some valid interpretations of its potential effect. All 6 cases had a cancer diagnosis with poor prognosis. Despite the presence of some confounding variables, it seems that the Gerson regimen has supported patients to some extent both physically and psychologically. More scientific attention needs to be directed to this area so that patients can practice safe and appropriate therapies that are based on evidence rather than anecdotes.
The Role of Zyflamend, an Herbal Anti-inflammatory, as a Potential Chemopreventive Agent Against Prostate Cancer: A Case Report
Authors: Rafailov Samuil , Cammack Sam , Stone Brian A. , Katz Aaron E.
Published: March 2007

Correlation between dietary intake and occurrence of prostate cancer has gained significant support in recent years. Although a direct correlation has yet to be proven between inflammation and prostate cancer, chronic or recurrent inflammation has been hypothesized to be the major predisposing factor for this disease. The authors have been studying Zyflamend, a novel herbal anti-inflammatory mixture, as a potential chemopreventive agent in a phase 1 trial for patients diagnosed with prostatic intraepithelial neoplasia. They report the results of the first patient who has completed the 18-month study in which 24 patients were assigned to a cohort and placed on successive herbal supplement regimen starting with Zyflamend alone.
Integrating Chinese and Conventional Medicine in Colorectal Cancer Treatment
Authors: Lahans Tai
Published: March 2007

The Chinese have been integrating cancer treatment for the past 60 years. Using conventional and Chinese traditional medicine, this integration has evolved into a sophisticated hybrid of medicine that has generated a great deal of well-designed research demonstrating that the use of combined care can improve outcomes for patients with cancer. This article seeks to explain the integration in terms of treatment of colorectal cancer and a colorectal cancer case with Duke's stage C adenocarcinoma.
The Lincoln Middle School Paradigm Shift
Authors: Maninger Robert M. , Powell Dan
Published: March 2007

This case study is presented for use with graduate students in educational administration. The intent is to further those students’ preparation to deal with cultural and organizational change, along with the examination of the role of the administrative team as instructional leaders. One of the primary roles of the building principal is to be the instructional leader and create a climate that is conducive to learning. The scenario for this case is built around a negative atmosphere that will require campus-level administrators to transform the campus into a high-performing school in a brief period of time.
Religious Garb
Authors: Meixsell Susanne H. , Zirkel Perry A.
Published: March 2007

Madeline Smith, a new elementary principal in northeastern Pennsylvania, wrestles with how to handle a dilemma involving one of her special education teachers who is wearing a head wrap while working. Wearing the head wrap is a violation of district policy, and if the head wrap is a religious symbol, then the employee is also violating the state religious garb statute. She must follow the district’s supervisory procedures when an employee is violating school policy, but she is unsure how her decision will affect staff morale and how much harm is actually occurring.
Human platelets synthesize and express functional tissue factor
Authors: Panes Olga , Matus Valeria , Sáez Claudia G. , Quiroga Teresa , Pereira Jaime , Mezzano Diego
Published: March 2007

The source and significance of bloodborne tissue factor (TF) are controversial. TF mRNA, protein, and TF-dependent procoagulant activity (PCA) have been detected in human platelets, but direct evidence of TF synthesis is missing. Nonstimulated monocyte-free platelets from most patients expressed TF mRNA, which was enhanced or induced in all of them after platelet activation. Immunoprecipitation assays revealed TF protein (mainly of a molecular weight [Mr] of approximately 47 kDa, with other bands of approximately 35 and approximately 60 kDa) in nonstimulated platelet membranes, which also increased after activation. This enhancement was concomitant with TF translocation to the plasma membrane, as demonstrated by immunofluorescence–confocal microscopy and biotinylation of membrane proteins. Platelet PCA, assessed by factor Xa (FXa) generation, was induced after activation and was inhibited by 48% and 76% with anti-TF and anti-FVIIa, respectively, but not by intrinsic pathway inhibitors. Platelets incorporated [35S]-methionine into TF proteins with Mr of approximately 47 kDa, approximately 35 kDa, and approximately 60 kDa, more intensely after activation. Puromycin but not actinomycin D or DRB (5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole) inhibited TF neosynthesis. Thus, human platelets not only assemble the clotting reactions on their membrane, but also supply their own TF for thrombin generation in a timely and spatially circumscribed process. These observations simplify, unify, and provide a more coherent formulation of the current cell-based model of hemostasis.
Homeostatic expansion and repertoire regeneration of donor T cells during graft versus host disease is constrained by the host environment
Authors: Gorski Jack , Chen Xiao , Gendelman Mariya , Yassai Maryam , Krueger Ashley , Tivol Elizabeth , Logan Brent , Komorowski Richard , Vodanovic-Jankovic Sanja , Drobyski William R.
Published: March 2007

Graft versus host disease (GVHD) typically results in impaired T-cell reconstitution characterized by lymphopenia and repertoire skewing. One of the major causes of inadequate T-cell reconstitution is that T-cell survival and expansion in the periphery are impaired. In this report, we have performed adoptive transfer studies to determine whether the quantitative reduction in T-cell numbers is due to an intrinsic T-cell defect or whether the environmental milieu deleteriously affects T-cell expansion. These studies demonstrate that T cells obtained from animals with graft-versus-host disease (GVHD) are capable of significant expansion and renormalization of an inverted CD4/CD8 ratio when they are removed from this environment. Moreover, these cells can generate complex T-cell repertoires early after transplantation and are functionally competent to respond to third-party alloantigens. Our data indicate that T cells from mice undergoing GVHD can respond to homeostatic signals in the periphery and are not intrinsically compromised once they are removed from the GVHD environment. We thereby conclude that the host environment and not an intrinsic T-cell defect is primarily responsible for the lack of effective T-cell expansion and diversification of complex T-cell repertoires that occurs during GVHD.
Quantifying the metabolic capabilities of engineered Zymomonas mobilis using linear programming analysis
Authors: Tsantili Ivi C , Karim M Nazmul , Klapa Maria I
Published: March 2007

Background

The need for discovery of alternative, renewable, environmentally friendly energy sources and the development of cost-efficient, "clean" methods for their conversion into higher fuels becomes imperative. Ethanol, whose significance as fuel has dramatically increased in the last decade, can be produced from hexoses and pentoses through microbial fermentation. Importantly, plant biomass, if appropriately and effectively decomposed, is a potential inexpensive and highly renewable source of the hexose and pentose mixture. Recently, the engineered (to also catabolize pentoses) anaerobic bacterium Zymomonas mobilis has been widely discussed among the most promising microorganisms for the microbial production of ethanol fuel. However, Z. mobilis genome having been fully sequenced in 2005, there is still a small number of published studies of its in vivo physiology and limited use of the metabolic engineering experimental and computational toolboxes to understand its metabolic pathway interconnectivity and regulation towards the optimization of its hexose and pentose fermentation into ethanol.

Results

In this paper, we reconstructed the metabolic network of the engineered Z. mobilis to a level that it could be modelled using the metabolic engineering methodologies. We then used linear programming (LP) analysis and identified the Z. mobilis metabolic boundaries with respect to various biological objectives, these boundaries being determined only by Z. mobilis network's stoichiometric connectivity. This study revealed the essential for bacterial growth reactions and elucidated the association between the metabolic pathways, especially regarding main product and byproduct formation. More specifically, the study indicated that ethanol and biomass production depend directly on anaerobic respiration stoichiometry and activity. Thus, enhanced understanding and improved means for analyzing anaerobic respiration and redox potential in vivo are needed to yield further conclusions for potential genetic targets that may lead to optimized Z. mobilis strains.

Conclusion

Applying LP to study the Z. mobilis physiology enabled the identification of the main factors influencing the accomplishment of certain biological objectives due to metabolic network connectivity only. This first-level metabolic analysis model forms the basis for the incorporation of more complex regulatory mechanisms and the formation of more realistic models for the accurate simulation of the in vivo Z. mobilis physiology.
Island-wide diversity in single nucleotide polymorphisms of the Plasmodium vivax dihydrofolate reductase and dihydropteroate synthetase genes in Sri Lanka
Authors: Schousboe Mette L , Rajakaruna Rupika S , Salanti Ali , Hapuarachchi Hapuarachchige C , Galappaththy Gawrie NL , Bygbjerg Ib C , Amerasinghe Priyanie H , Konradsen Flemming , Alifrangis Michael
Published: March 2007

Background

Single nucleotide polymorphisms (SNPs) in the Plasmodium vivax dihydrofolate reductase (Pfdhfr) and dihydropteroate synthetase (Pvdhps) genes cause parasite resistance to the antifolate drug combination, sulphadoxine/pyrimethamine (SP). Monitoring these SNPs provide insights into the level of drug pressure caused by SP use and presumably other antifolate drugs. In Sri Lanka, chloroquine (CQ) with primaquine (PQ) and SP with PQ is used as first and second line treatment, respectively, against uncomplicated Plasmodium falciparum and/or P. vivax infections. CQ/PQ is still efficacious against P. vivax infections, thus SP is rarely used and it is assumed that the prevalence of SNPs related to P. vivax SP resistance is low. However, this has not been assessed in Sri Lanka as in most other parts of Asia. This study describes the prevalence and distribution of SNPs related to P. vivax SP resistance across Sri Lanka.

Subjects and methods

P. vivax- positive samples were collected from subjects presenting at government health facilities across nine of the major malaria endemic districts on the island. The samples were analysed for SNPs/haplotypes at codon 57, 58, 61 and 117 of the Pvdhfr gene and 383, 553 and 585 of the Pvdhps gene by applying PCR followed by a hybridization step using sequence specific oligonucleotide probes (SSOPs) in an ELISA format.

Results

In the study period, the government of Sri Lanka recorded 2,149 P. vivax cases from the nine districts out of which, 454 (21.1%) blood samples were obtained. Pvdhfr haplotypes could be constructed for 373 of these. The FSTS wild-haplotype was represented in 257 samples (68.9%), the double mutant LRTS haplotype was the most frequently observed mutant (24.4%) while the triple mutation (LRTN) was only identified once. Except for two samples of the single mutated Pvdhps GAV haplotype, the remaining samples were wildtype. Geographical differences were apparent, notably a significantly higher frequency of mutant Pvdhfr haplotypes was observed in the Northern districts.

Conclusion

Since SP is rarely used in Sri Lanka, the high frequency and diversity of Pvdhfr mutations was unexpected indicating the emergence of drug resistant parasites despite a low level of SP drug pressure.
The role of MUC1 and MUC3 in the biology and prognosis of colorectal cancer
Authors: Duncan Timothy J , Watson Nicholas FS , Al-Attar Ahmad H , Scholefield John H , Durrant Lindy G
Published: March 2007

Background

MUC1 and MUC3 are from a large family of glycoproteins with an aberrant expression profile in various malignancies. Much interest has been focused on the role of these proteins in the development and progression of colorectal cancer; however, no previous studies have included the highly confounding variable of vascular invasion in their survival analysis. Using high throughput tissue microarray technology we assessed the prognostic value of MUC1 and MUC3 expression in the largest cohort of colorectal cancer patients to date. We propose that tumours lacking expression of MUC1 and MUC3 will be more likely to metastasise, due to previously observed loss of cell-cell adhesion, and this will therefore lead to more aggressive cancers with poorer prognosis.

Methods

A tissue micro-array was prepared from tumour samples of 462 consecutive patients undergoing resection of a primary colorectal cancer. A comprehensive prospectively recorded data base with mean follow up of 75 months was collected and included common clinicopathological variables and disease specific survival. Immunohistochemical analysis of MUC1 and MUC3 expression was performed using antibodies NCL-MUC1 and 1143/B7 respectively, results were correlated with the variables within the database.

Results

Positive expression of MUC1 and MUC3 was seen in 32% and 74% of tumours respectively. On univariate analysis no correlation was seen with either MUC1 or MUC3 and any of the clinicopathological variables including tumour grade and stage, vascular invasion and tumour type. Kaplan-Meier analysis demonstrated a significant reduction in disease specific survival with MUC1 positive tumours (p = 0.038), this was not seen with MUC3 (p = 0.552). On multivariate analysis, using Cox proportional hazards model, MUC1 expression was shown to be an independent marker of prognosis (HR 1.339, 95%CI 1.002–1.790, p = 0.048).

Conclusion

MUC1 expression in colorectal cancer is an independent marker of poor prognosis, even when vascular invasion is included in the analysis. These results support previous studies suggesting a role for MUC1 in colorectal cancer development possibly through its effects on cell adhesion.
The MAP kinase HwHog1 from the halophilic black yeast Hortaea werneckii: coping with stresses in solar salterns
Authors: Lenassi Metka , Vaupotic Tomaz , Gunde-Cimerman Nina , Plemenitas Ana
Published: March 2007

Background

Hortaea werneckii is one of the most salt-tolerant species among microorganisms. It has been isolated from hypersaline waters of salterns as one of the predominant species of a group of halophilic and halotolerant melanized yeast-like fungi, arbitrarily named as "black yeasts". It has previously been shown that H. werneckii has distinct mechanisms of adaptation to high salinity environments that are not seen in salt-sensitive and only moderately salt-tolerant fungi. In H. werneckii, the HOG pathway is important for sensing the changes in environmental osmolarity, as demonstrated by identification of three main pathway components: the mitogen-activated protein kinase (MAPK) HwHog1, the MAPK kinase HwPbs2, and the putative histidine kinase osmosensor HwHhk7.

Results

In this study, we show that the expression of HwHOG1 in salt-adapted cells depends on the environmental salinity and that HwHOG1 transcription responds rapidly but reciprocally to the acute hyper-saline or hypo-saline stress. Molecular modelling of HwHog1 reveals an overall structural homology with other MAPKs. HwHog1 complements the function of ScHog1 in the Saccharomyces cerevisiae multistress response. We also show that hyper-osmolar, oxidative and high-temperature stresses activate the HwHog1 kinase, although under high-temperature stress the signal is not transmitted via the MAPK kinase Pbs2. Identification of HOG1-like genes from other halotolerant fungi isolated from solar salterns demonstrates a high degree of similarity and excellent phylogenetic clustering with orthologues of fungal origin.

Conclusion

The HOG signalling pathway has an important role in sensing and responding to hyper-osmolar, oxidative and high-temperature stresses in the halophilic fungi H. werneckii. These findings are an important advance in our understanding of the HOG pathway response to stress in H. werneckii, a proposed model organism for studying the salt tolerance of halophilic and halotolerant eukaryotes.
Glutamine induces heat-shock protein and protects against Escherichia coli lipopolysaccharide-induced vascular hyporeactivity in rats
Authors: Jing Liang , Wu Qiong , Wang Fuzhou
Published: March 2007

Introduction

Vascular hyporeactivity is an important problem associated with sepsis. Although the mechanism involves inflammatory pathway activation, specific therapeutic approaches have not been defined. Glutamine (Gln) has been shown to provide some anti-inflammatory effects and improve outcomes in sepsis. Here, we tested the hypothesis that Gln could reduce Escherichia coli lipopolysaccharide (LPS)-induced vascular hyporeactivity and evaluated the role of heat-shock protein 70 (HSP70) induction in this process.

Methods

Twenty-four male Sprague-Dawley rats were divided into control, LPS shock, and alanyl-Gln dipeptide+LPS shock (Ala-Gln+LPS) groups. Six hours after administration of LPS, phenylephrine (PE) (0.5 to approximately 2.5 μg/kg) was applied intravenously to all groups, and the percentage increase in mean arterial pressure (MAP) was detected in the respective groups. The concentration-response curve of PE was obtained in tension experiments, and the average values of PE maximum efficacy (Emax) and median effective dose (EC50) were calculated. The plasma concentrations of malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) were detected in all groups. The expressions of HSP70 from heart, liver, lung, and aorta were also assayed in all groups.

Results

The maximal percentage increase in MAP induced by PE was significantly reduced to 12.7% in the LPS shock group (P < 0.05) and was restored to 15.6% in the Ala-Gln+LPS group (P < 0.05), whereas the control group was 24.7%. The average values of PE Emax and EC50 were significantly impaired in the LPS shock group (P < 0.05) but partially restored in the Ala-Gln+LPS group (P < 0.05). The expressions of HSP70 from the heart, aorta, lung, and liver were much higher in the Ala-Gln+LPS group than those in the LPS shock group (P < 0.05). The plasma concentrations of TNF-α, IL-6, and MDA were much lower in the Ala-Gln+LPS group than those in the LPS shock group.

Conclusion

Gln effectively improves vascular reactivity by inducing the expression of HSP70, reducing inflammatory cytokine release and peroxide biosynthesis in LPS shock rats. These results suggest that Gln has a potentially beneficial therapeutic effect for septic shock patients.