bluuebunny/crossref_metadata_2025 huggingface dataset:
The Mesoscale Characteristics of Tropical Oceanic Precipitation during Kelvin and Mixed Rossby–Gravity Wave Events
Authors: Holder Christopher T. , Yuter Sandra E. , Sobel Adam H. , Aiyyer Anantha R.
Published: January 2008

Precipitation structures within Kelvin and mixed Rossby–gravity (MRG) wave troughs near Kwajalein Atoll during the 1999–2003 rainy seasons are analyzed using three-dimensional ground-based radar data and upper-air sounding data. Consistent with previous work, wave troughs are preferred locations for precipitation and typically yield 1.3 times more rain area compared to the overall rainy season climatology.

Although the contiguous areas of cold cloudiness associated with tropical wave troughs are large and long lived, the underlying precipitation structure is most frequently small, isolated convection from mixed-phase clouds. This mismatch in instantaneous cold cloudiness area versus radar-observed precipitation area indicates differences in the rate and nature of evolution between the mesoscale anvil cloud and the underlying precipitating portion of the cloud.

Mesoscale convective systems (MCSs) were identified during portions of 32 of the 39 wave trough events examined. Convective cells are frequently embedded within stratiform regions. Reflectivity holes or pores in contiguous radar echo have been frequently observed in other regions but are quantified for the first time in this study. Based on characteristics such as total size of precipitating area and occurrence of convective lines, MCSs within Kelvin troughs are slightly more organized than those occurring within MRG troughs.

Similar to the west Pacific warm pool region, there is a well-defined separation between observed and unobserved stratiform area fraction and convective precipitation area, each as a function of total precipitation area. At precipitation area sizes near 40% of the radar domain, the maximum observed convective area changes from increasing to decreasing with increasing precipitation area. The maximum observed convective precipitation area occupied ∼20% of the radar domain. These characteristics suggest that the atmosphere in the west Pacific can sustain a limited area of updrafts capable of supporting precipitation growth by collision/coalescence and riming.
Markov Chain Modeling of Sequences of Lagged NWP Ensemble Probability Forecasts: An Exploration of Model Properties and Decision Support Applications
Authors: McLay Justin G.
Published: January 2008

It is shown that sequences of lagged ensemble-derived probability forecasts can be treated as being realizations of a discrete, finite-step Markov chain. A reforecast ensemble dataset is used to explore this idea for the case in which the Markov chain has 12 states and 15 steps and the probability forecasts are for the event for which the 500-hPa geopotential height exceeds the climatological value at a specified point. Results suggest that the transition probabilities of the Markov chain are best modeled as first order if they are obtained from the reforecast ensemble dataset using maximum likelihood estimation. Most of the first-order-estimated transition probabilities are statistically significant. Also, the transition probabilities are inhomogeneous, and all states in the chain communicate. A variety of potential decision support applications for the Markov chain parameters are highlighted. In particular, the transition probabilities allow calculation of the conditional probability of taking protective action and calculation of the conditional expected expense when used with static cost–loss decision models. Also, the transition probabilities facilitate optimized decisions when incorporated into dynamic decision models. Decision model test scenarios can be obtained using cluster analysis and conditional most likely sequences, and these scenarios reveal the key patterns traced by the Markov chain.
Forecasting the Swiss economy using VECX models: An exercise in forecast combination across models and observation windows
Authors: Assenmacher-Wesche Katrin , Pesaran M. Hashem
Published: January 2008

This paper uses vector error correction models of Switzerland for forecasting output, inflation and the short-term interest rate. It considers three different ways of dealing with forecast uncertainties. First, it investigates the effect on forecasting performance of averaging over forecasts from different models. Second, it considers averaging forecasts from different estimation windows. It is found that averaging over estimation windows is at least as effective as averaging over different models and both complement each other. Third, it examines whether using weighting schemes from the machine learning literature improves the average forecast. Compared to equal weights the effect of alternative weighting schemes on forecast accuracy is small in the present application.
Bridging the Divide
Authors: Kalu Kalu N.
Published: January 2008

This article addresses emerging issues of the new administrative state, international governance, and the development of an institutional capacity for coordinating multiple layers of demand in a dynamic and uncertain global environment. The argument is made for a curricular redesign in the context of a transformative public administration and the development of a new model of integrated military education (inside-out-coherence) for resolving emergent problems of coordination, adaptation, and functional interdependence. The notion of inside-out-coherence is that soldiers (even though they are trained for warfare) should also be availed of critical political as well as administrative knowledge. The new military and public administrator will need to be functionally versatile, must become a master of many roles (technical, political, cultural), and must be able to innovate as well as adapt to the fluid nature of international politics. A new kind of learning is required, but how benign would it be?
Information Technology Employees in State Government
Authors: Reid Margaret F. , Riemenschneider Cynthia K. , Allen Myria W. , Armstrong Deborah J.
Published: January 2008

This article explores the affective organizational commitment, job involvement, and job satisfaction of an increasingly important segment of the public sector workforce: information technology (IT) employees in state government. We propose a model that explores job characteristics and work experiences variables that together influence affective organizational commitment, job satisfaction, and job involvement. Using canonical correlation analysis, we find that role ambiguity, perceived organizational support, leader—member exchange, and task variety are the independent variables that together explain most of the variance in the affective organizational commitment and job satisfaction of IT employees working for one-state government. In contrast to findings based on private sector IT employees, our analysis does not identify major gender differences. Taken together, these findings advance our understanding of affective commitment and job satisfaction within the public sector and provide agency managers actionable ideas on how to retain valuable IT employees.
The Feasibility and Effectiveness of Translating a Matter of Balance Into a Volunteer Lay Leader Model
Authors: Healy Tara C. , Peng Cheng , Haynes Margaret S. , McMahon Elaine M. , Botler Joel L. , Gross Laurence
Published: February 2008

The purpose of this study is to examine whether A Matter of Balance, a cognitive-behavioral program previously found to be efficacious in a randomized clinical trial (RCT), could be translated into a community-based volunteer lay leader model and achieve outcomes comparable to those found in the RCT. A repeated measures, single-group design is employed. Participants experience significant increases in falls efficacy, falls management, and falls control at 6 weeks, 6 months, and 12 months, thus achieving comparable outcomes with those of participants in the RCT. This successful translation of a professionally led health promotion program into a volunteer lay leader model enables embedding the program in community-based organizations, thus making it more broadly available to older adults in diverse settings. The findings also suggest that other evidence-based programs currently requiring professional staff can be adapted for facilitation by volunteers.
Vein of Galen Aneurysmal Malformation With Deep Venous Communication and Subarachnoid Hemorrhage
Authors: Abend Nicholas S. , Ichord Rebecca , Aijun Zhang  , Hurst Robert
Published: January 2008

A previously healthy 2-year-old boy presented with the acute onset of left middle cerebral artery syndrome. Evaluation revealed subarachnoid hemorrhage and a vein of Galen aneurysmal malformation with angiographic reflux into the deep venous system. Analysis of the angioarchitecture of the lesion demonstrated the basis of the hemorrhage to be reflux into cortical veins. The case supports and underscores the clinical relevance of recent reports indicating that the venous drainage of a vein of Galen aneurysmal malformation may communicate with the normal deep venous system. Such a communication implies that endovascular or surgical obliteration of the venous side of a vein of Galen aneurysmal malformation may impair normal venous drainage, potentially resulting in a venous infract or hemorrhage.
Mowat-Wilson Syndrome Affecting 3 Siblings
Authors: Ohtsuka Motoko , Oguni Hirokazu , Ito Yasushi , Nakayama Tomohiro , Matsuo Mari , Osawa Makiko , Saito Kayoko , Yamada Yasukazu , Wakamatsu Nobuaki
Published: January 2008

We herein report 3 cases of Mowat-Wilson syndrome, characterized by distinct facial features, severe psychomotor retardation, and epilepsy, recurring in 3 siblings from the same parents. The proband was a 15-month-old boy, the youngest of 3 children (2 elder sisters), who was referred to our hospital for the treatment of severe seizures. The clinical features and course of these 3 siblings were compatible with those of previously reported Mowat-Wilson syndrome patients, and all siblings had the same E87X nonsense mutation in ZFHX1B, whereas their mother did not show the mutation. Because Mowat-Wilson syndrome has been caused by de novo mutation in ZF HX1B, germ-line mosaicism should be considered if recurrence in siblings is observed.
Haddad Syndrome: A Case of an Infant With Central Congenital Hypoventilation Syndrome and Hirschsprung Disease
Authors: Lai Daniel , Schroer Brian
Published: January 2008

This report presents an otherwise healthy infant who developed unexplained apnea and long-segment Hirschsprung disease. After extensive evaluation that included a paired-like homeobox 2b gene ( PHOX2B) analysis, he was found to have Haddad syndrome, a congenital disorder that features central congenital hypoventilation syndrome in conjunction with Haddad syndrome. Recent work has associated polyalanine repeats within the PHOX2B gene on chromosome 4p12 with central congenital hypoventilation syndrome, whereas PHOX2B knockout mice develop aganglionic bowels.
The Role of State Programs in NIBRS Data Quality
Authors: Barnett-Ryan Cynthia , Swanson Gregory
Published: January 2008

This study explores the question of how the organization of state programs might positively influence the data quality of the state's incident-based reporting data and its National Incident-Based Reporting System (NIBRS) data submissions. To investigate this topic, the programs of two states (Tennessee and Vermont) identified as adept at resolving data quality issues are described. These descriptions show that these two state programs have taken measures to implement the quality assurance programs and procedures recommended in The Blueprint for the Future of the Uniform Crime Reporting Program: Final Report of the UCR Study. Given that some states have undertaken very different and very aggressive quality control programs, subsequent research should be done to assess the effects of these programs on the quality of NIBRS submissions.
East, Left Behind: Picturing Second Geography
Authors: Sirin Bugrahan
Published: January 2008

In almost every case, socialism left behind a neglected geography, ruined industrial landscapes, masses of unsustainable urban structures, and finally, the unnatural application of an ideology into the built environment. However, only after a dozen years did people realize it was not only the physical that had been neglected; it was also the individual efforts of the citizens that were being ignored. These two things together brought pessimistic side effects into these societies. Former German Democratic Republic lands still struggle with a seemingly physical crisis, but below the surface lies a mental crisis.
A Retrospective Review of Immediate Weightbearing After First Metatarsophalangeal Joint Arthrodesis
Authors: Berlet Gregory C. , Hyer Christopher F. , Glover Jason P.
Published: January 2008

First metatarsophalangeal (MTP) joint arthrodesis is a proven technique as a salvage procedure for many foot pathologies. Many studies have looked at joint preparation techniques, position of the fusion, and construct stability. In this retrospective study, the authors report the overall fusion rate after first MTP joint fusion with full immediate postoperative weightbearing. Forty-five first MTP arthrodeses were performed during the study period. Eight fusions were excluded, leaving 37 fusions for review. The overall fusion rate was 91.1%. The mean time to fusion was 69.0 ± 37.6 days. Complications included 2 delayed unions (1 screw, 1 plate), 3 nonunions (1 screw, 2 plates), and 2 hardware removals (1 screw, 1 plate). Fixation stability is important to allow immediate postoperative weightbearing. A fusion rate of 91.1% was seen in a diversity of patients after first MTP fusion with immediate weightbearing.
The Practical Application of Multimedia Technology to Facilitate the Education and Treatment of Patients With Plantar Fasciitis: A Pilot Study
Authors: Beischer Andrew Donald , Clarke Andrew , de Steiger Richard Noel , Donnan Leo , Ibuki Aileen , Unglik Rebecca
Published: January 2008

This study was designed to evaluate the efficacy of a multimedia patient education module when incorporated into the standard treatment protocol for patients diagnosed with plantar fasciitis. A thorough, standardized surgeon-patient education discourse took place following diagnosis. At the conclusion of the consultation, patients viewed the multimedia module. Questionnaires designed to assess understanding and satisfaction with information delivery were completed by patients following the consultation and again after viewing the module. Forty-one patients participated in the study. After viewing the module, patients achieved an average of 87% correct responses on the knowledge questionnaire, a significant improvement (P < .0001) over the 64% achieved following the surgeon-patient discourse. Ease of understanding of the information delivered by the module was rated significantly better (P < .0001) than the surgeon-patient discourse. Ninety-eight percent of patients indicated they felt well informed about plantar fasciitis following viewing the module compared with 68% following the surgeon-patient discourse. Sixty-three percent of patients indicated that the module best answered their questions, 7% preferred the surgeon, and 30% rated both equally. Multimedia plantar fasciitis educational material improved patient understanding of the standard treatment protocol and satisfaction with the information delivery in an orthopedic private practice.
Spinning Debates: The Impact of the News Media's Coverage of the Final 2004 Presidential Debate
Authors: Fridkin Kim L. , Kenney Patrick J. , Gershon Sarah Allen , Serignese Woodall Gina
Published: January 2008

We demonstrate that the news media's “spin” or analysis following the last presidential debate in 2004 influenced citizens' evaluations of the candidates. The media's “instant analyses” in the twenty-four hours following the debate was decidedly one-sided, favoring President Bush more than Senator Kerry. We show that the news media's spin persuaded potential voters to alter their attitudes regarding the competing candidates. We rely on a multimethodological approach, including an experiment with a quasi-experimental component, a public opinion survey, and a content analysis. To examine the media's spin, we conducted a content analysis of news coverage on television, on the Internet, and in newspapers for the twenty-four hours following the final 2004 presidential debate. Second, to examine how citizens reacted to the media's coverage, we relied on a representative public opinion survey conducted immediately following the debate. In addition, we conducted an experiment where certain individuals were exposed to the debate, while others were not, and we tracked these subjects over the course of a week to determine the stability of their attitudes in the midst of intense media coverage.
EBV LMP2A affects LMP1-mediated NF-κB signaling and survival of lymphoma cells by regulating TRAF2 expression
Authors: Guasparri Ilaria , Bubman Darya , Cesarman Ethel
Published: January 2008

A mechanism used by Epstein-Barr virus (EBV) for in vitro transformation of B cells into lymphoblastoid cell lines (LCLs) is activation of the NF-κB pathway, which is largely mediated by the EBV latent membrane protein 1 (LMP1). LMP1 is coexpressed with LMP2A in many EBV-associated lymphoid malignancies. Since inhibition of NF-κB leads to apoptosis of EBV-infected LCLs and lymphoma cell lines, we sought to determine whether LMP1 alone, or in combination with other viral proteins, is responsible for initiating NF-κB activation in these cells, thereby playing a role in cell survival. We found that suppression of LMP1 by RNA interference results in inhibition of basal NF-κB and induction of apoptosis. Unexpectedly, knockdown of LMP2A also resulted in comparable decrease of NF-κB activity and apoptosis. We report that LMP2A protein controls the expression of TRAF2 mRNA, which in turn is necessary for signaling by LMP1. Our data contrast with previous studies showing that transfected LMP1 can signal in the absence of LMP2A or TRAF2, and demonstrate that both LMP2A and TRAF2 are required for survival in naturally infected lymphoma cells and LCLs. These results also support LMP1, LMP2A, and TRAF2 as potential therapeutic targets in a subset of EBV-associated lymphoid malignancies.
Human antibody RNase fusion protein targeting CD30+ lymphomas
Authors: Menzel Christian , Schirrmann Thomas , Konthur Zoltan , Jostock Thomas , Dübel Stefan
Published: January 2008

Targeted RNases (TRs) are immunoenzymes with ribonucleases as cytotoxic effector domains, which are less immunogenic as plant or bacterial toxin components of classical immunotoxins. In this study, we show the generation and production of the first entirely human TR (huTR) directed against CD30+ lymphomas. The scFv-Fc-RNase construct was produced in human embryonic kidney (HEK) 293T cells, yielding up to 4 mg/L soluble protein after purification by protein A affinity chromatography. Size exclusion chromatography revealed a homodimer of the predicted molecular mass. Surface plasmon resonance analysis revealed an affinity to CD30 of KD of less than 1 nM for both the scFv-Fc and the scFv-Fc-RNase proteins. Internalization of the scFv-Fc-RNase protein by CD30+ Karpas-299 cells was demonstrated by confocal microscopy. Proliferation of the CD30+ lymphoma cell line Karpas-299 was strongly inhibited by CD30-specific huTR protein (IC50 = 3.3 nM). The huTR is a promising candidate for the immunotherapy of CD30+ lymphomas because of its expected low immunogenicity, good production yields, and potent effector function upon target cell binding and internalization. Its modular design is set to target other internalizing tumor antigens using different antibody domains.
Components of the ubiquitin-proteasome pathway compete for surfaces on Rad23 family proteins
Authors: Goh Amanda M , Walters Kylie J , Elsasser Suzanne , Verma Rati , Deshaies Raymond J , Finley Daniel , Howley Peter M
Published: January 2008

Background

The delivery of ubiquitinated proteins to the proteasome for degradation is a key step in the regulation of the ubiquitin-proteasome pathway, yet the mechanisms underlying this step are not understood in detail. The Rad23 family of proteins is known to bind ubiquitinated proteins through its two ubiquitin-associated (UBA) domains, and may participate in the delivery of ubiquitinated proteins to the proteasome through docking via the Rad23 ubiquitin-like (UBL) domain.

Results

In this study, we investigate how the interaction between the UBL and UBA domains may modulate ubiquitin recognition and the delivery of ubiquitinated proteins to the proteasome by autoinhibition. We have explored a competitive binding model using specific mutations in the UBL domain. Disrupting the intramolecular UBL-UBA domain interactions in HHR23A indeed potentiates ubiquitin-binding. Additionally, the analogous surface on the Rad23 UBL domain overlaps with that required for interaction with both proteasomes and the ubiquitin ligase Ufd2. We have found that mutation of residues on this surface affects the ability of Rad23 to deliver ubiquitinated proteins to the proteasome.

Conclusion

We conclude that the competition of ubiquitin-proteasome pathway components for surfaces on Rad23 is important for the role of the Rad23 family proteins in proteasomal targeting.
Development and evaluation of one step single tube multiplex RT-PCR for rapid detection and typing of dengue viruses
Authors: Saxena Parag , Dash Paban Kumar , Santhosh SR , Shrivastava Ambuj , Parida Manmohan , Rao PV Lakshmana
Published: January 2008

Background

Dengue is emerging as a major public health concern in many parts of the world. The development of a one-step, single tube, rapid, and multiplex reverse transcription polymerase chain reaction (M-RT-PCR) for simultaneous detection and typing of dengue virus using serotype specific primers during acute phase of illness is reported.

Results

An optimal assay condition with zero background was established having no cross-reaction with closely related members of flavivirus (Japanese encephalitis, West Nile, Yellow fever) and alphavirus (Chikungunya). The feasibility of M-RT-PCR assay for clinical diagnosis was validated with 620 acute phase dengue patient sera samples of recent epidemics in India. The comparative evaluation vis a vis conventional virus isolation revealed higher sensitivity. None of the forty healthy serum samples screened in the present study revealed any amplification, thereby establishing specificity of the reported assay for dengue virus only.

Conclusion

These findings clearly suggested that M-RT-PCR assay reported in the present study is the rapid and cost-effective method for simultaneous detection as well as typing of the dengue virus in acute phase patient serum samples. Thus, the M-RT-PCR assay developed in this study will serve as a very useful tool for rapid diagnosis and typing of dengue infections in endemic areas.
Role of resistin as a marker of inflammation in systemic lupus erythematosus
Authors: Almehed Katarina , d'Elia Helena Forsblad , Bokarewa Maria , Carlsten Hans
Published: January 2008

Introduction

Resistin is a cystein-rich secretory adipokine. It is proposed to have proinflammatory properties in humans. The aim of this study was to determine associations between serum levels of resistin and markers of inflammation and bone mineral density (BMD) in female patients with systemic lupus erythematosus (SLE).

Methods

One hundred sixty-three female patients with SLE (20 to 82 years old) were examined in a cross-sectional study. Venous blood samples were analyzed for resistin, erythrocyte sedimentation rate (ESR), C-reactive protein, creatinine, fasting lipids, complements, tumor necrosis factor-alpha, interleukin (IL)-1β, IL-6, sIL-6R (soluble IL-6 receptor), ICTP (C-terminal telopeptide of type I collagen), and PINP (N-terminal propeptide of type I procollagen). Simple and multiple regression analyses as well as logistic regression analyses were performed. Resistin in serum was compared with 42 healthy female controls with respect to age.

Results

Serum resistin levels in controls were similar to those of patients with SLE. Markers of inflammation and current dose of glucocorticosteroids correlated positively to resistin in serum. Markers of renal function, number of prevalent vertebral fractures, and BMD were also significantly associated with resistin. In a multiple regression model, ESR, creatinine, C3, current glucocorticosteroid dose, high-density lipoprotein, and BMD radius remained significantly associated with resistin. In logistic regression analyses with resistin as the independent variable, a significant association was found with ESR (normal or elevated) but not with S-creatinine or z score for hip and radius total.

Conclusion

Although resistin measurements did not differ between patients and controls, resistin was clearly associated with general inflammation, renal disease, treatment with glucocorticosteroids, and bone loss. We hypothesize that resistin has proinflammatory and disease-promoting properties in SLE. Further studies are needed to elucidate the mechanism behind these associations.
Quantitative methods for genome-scale analysis of in situ hybridization and correlation with microarray data
Authors: Lee Chang-Kyu , Sunkin Susan M , Kuan Chihchau , Thompson Carol L , Pathak Sayan , Ng Lydia , Lau Chris , Fischer Shanna , Mortrud Marty , Slaughterbeck Cliff , Jones Allan , Lein Ed , Hawrylycz Michael
Published: January 2008

With the emergence of genome-wide colorimetric in situ hybridization (ISH) data sets such as the Allen Brain Atlas, it is important to understand the relationship between this gene expression modality and those derived from more quantitative based technologies. This study introduces a novel method for standardized relative quantification of colorimetric ISH signal that enables a large-scale cross-platform expression level comparison of ISH with two publicly available microarray brain data sources.
Premature Ovarian Failure and Its Consequences: Vasomotor Symptoms, Sexuality, and Fertility
Authors: Schover Leslie R.
Published: February 2008

Premature ovarian failure is a common consequence of systemic treatment for premenopausal breast cancer. Vasomotor symptoms and sexual dysfunction occur frequently in women who have an abrupt menopause from chemotherapy or ovarian suppression. However, current fertility may be impaired even in women who are menstruating after chemotherapy, and survivors are at high risk for permanent ovarian failure at a young age. Hot flashes can be managed with venlaxafine, gabapentin, or—potentially—stress management. Providing advice on treating vaginal dryness and brief sexual counseling can often alleviate sexual dysfunction. Options for fertility preservation remain limited but are improving rapidly. Distress about interrupted childbearing has a long-term impact on the quality of life.
Incidence Trends for Human Papillomavirus–Related and –Unrelated Oral Squamous Cell Carcinomas in the United States
Authors: Chaturvedi Anil K. , Engels Eric A. , Anderson William F. , Gillison Maura L.
Published: January 2008

Purpose

To investigate the impact of human papillomavirus (HPV) on the epidemiology of oral squamous cell carcinomas (OSCCs) in the United States, we assessed differences in patient characteristics, incidence, and survival between potentially HPV-related and HPV-unrelated OSCC sites.

Patients and Methods

Data from nine Surveillance, Epidemiology, and End Results program registries (1973 to 2004) were used to classify OSCCs by anatomic site as potentially HPV-related (n = 17,625) or HPV-unrelated (n = 28,144). Joinpoint regression and age-period-cohort models were used to assess incidence trends. Life-table analyses were used to compare 2-year overall survival for HPV-related and HPV-unrelated OSCCs.

Results

HPV-related OSCCs were diagnosed at younger ages than HPV-unrelated OSCCs (mean ages at diagnosis, 61.0 and 63.8 years, respectively; P < .001). Incidence increased significantly for HPV-related OSCC from 1973 to 2004 (annual percentage change [APC] = 0.80; P < .001), particularly among white men and at younger ages. By contrast, incidence for HPV-unrelated OSCC was stable through 1982 (APC = 0.82; P = .186) and declined significantly during 1983 to 2004 (APC = −1.85; P < .001). When treated with radiation, improvements in 2-year survival across calendar periods were more pronounced for HPV-related OSCCs (absolute increase in survival from 1973 through 1982 to 1993 through 2004 for localized, regional, and distant stages = 9.9%, 23.1%, and 18.6%, respectively) than HPV-unrelated OSCCs (5.6%, 3.1%, and 9.9%, respectively). During 1993 to 2004, for all stages treated with radiation, patients with HPV-related OSCCs had significantly higher survival rates than those with HPV-unrelated OSCCs.

Conclusion

The proportion of OSCCs that are potentially HPV-related increased in the United States from 1973 to 2004, perhaps as a result of changing sexual behaviors. Recent improvements in survival with radiotherapy may be due in part to a shift in the etiology of OSCCs.
Clinical Application of the 70-Gene Profile: The MINDACT Trial
Authors: Cardoso Fatima , Van't Veer Laura , Rutgers Emiel , Loi Sherene , Mook Stella , Piccart-Gebhart Martine J.
Published: February 2008

The 70-gene profile is a new prognostic tool that has the potential to greatly improve risk assessment and treatment decision making for early breast cancer. Its prospective validation is currently ongoing through the MINDACT (Microarray in Node-Negative Disease May Avoid Chemotherapy) trial, a 6,000-patient randomized, multicentric trial. This article reviews the several steps in the development of the profile from its discovery to its clinical validation.
Sentinel Node Biopsy: Interpretation and Management of Patients With Immunohistochemistry-Positive Sentinel Nodes and Those With Micrometastases
Authors: Rutgers Emiel J.T.
Published: February 2008

The sentinel node procedure is an adequate tool to identify lymph node metastasis in breast cancer. Sentinel nodes are generally examined with greater attention mainly to exclude, as reliably as possible, lymph node metastasis. To achieve this, many protocols are used, resulting in different rates of micrometastasis or isolated tumor cells encountered. Since the prognostic significance of isolated tumor cells or micrometastasis in the sentinel nodes, and the risk of further axillary lymph node involvement in patients with isolated tumor cells, is uncertain and at most limited, these findings may pose difficulties for clinicians in clinical decision making. Protocols that identify lymph node metastasis, from which the clinical relevance is known, are warranted. Unnecessary lymph node dissections should be avoided.
Preoperative Therapy in Invasive Breast Cancer: Pathologic Assessment and Systemic Therapy Issues in Operable Disease
Authors: Gralow Julie R. , Burstein Harold J. , Wood William , Hortobagyi Gabriel N. , Gianni Luca , von Minckwitz Gunter , Buzdar Aman U. , Smith Ian E. , Symmans William F. , Singh Baljit , Winer Eric P.
Published: February 2008

Purpose

To review the state of the science with respect to preoperative systemic therapy and pathologic assessment in operable breast cancer.

Methods

This article reviews data presented at the National Cancer Institute State of the Science Conference on Preoperative Therapy in Invasive Breast Cancer as well as supporting published data.

Results

Preoperative chemotherapy in operable breast cancer has been shown to improve breast conservation rates as a result of tumor response to therapy. When patients are given preoperative systemic therapy, regimens should be the same as those established as safe and active in the adjuvant setting. At present, there are no data to suggest that systemic treatment should be tailored based on initial tumor response, or based on the extent of residual disease. In operable breast cancer, there seems to be no survival advantage from initiation of systemic therapy before surgery. A variety of clinical, imaging, and pathologic measurements are available to gauge tumor response to treatment. There is a clear correlation between tumor response in the breast and lymph nodes and both disease-free and overall survival. Pathologic complete response and other pathologic measures may be useful as surrogate end points in evaluating and understanding new therapies.

Conclusion

In operable breast cancer, preoperative systemic therapy is effective and can improve breast conservation rates. Unless the tumor is large or the patient is in a clinical trial, postoperative adjuvant systemic therapy is the standard of care. To achieve optimal outcomes, preoperative systemic therapy must be administered as part of a coordinated, multimodality treatment program. The preoperative setting provides a unique opportunity to study the impact of systemic therapies on breast cancer biology.
Functional interactions between phosphatase POPX2 and mDia modulate RhoA pathways
Authors: Xie Yi , Tan E-Jean , Wee Shimei , Manser Edward , Lim Louis , Koh Cheng-Gee
Published: January 2008

Rho GTPases and their downstream effectors regulate changes in the actin cytoskeleton that underlie cell motility and adhesion. They also participate, with RhoA, in the regulation of gene transcription by activating serum response factor (SRF)-mediated transcription from the serum response element (SRE). SRF-mediated transcription is also promoted by several proteins that regulate the polymerization or stability of actin. We have previously identified a family of PP2C phosphatases, POPXs, which can dephosphorylate the CDC42/RAC-activated kinase PAK and downregulate its enzymatic and actin cytoskeletal activity. We now report that POPX2 interacts with the formin protein mDia1 (DIAPH1). This interaction is enhanced when mDia1 is activated by RhoA. The binding of POPX2 to mDia1 or to an mDia-containing complex greatly decreases the ability of mDia1 to activate transcription from the SRE. We propose that the interaction between mDia1 and POPX2 (PPM1F) serves to regulate both the actin cytoskeleton and SRF-mediated transcription, and to link the CDC42/RAC1 pathways with those of RhoA.
Chemistry in Mega-gravity: Preparation of Molecular-scaled Graded Materials from Radical Copolymerization
Authors: Ihara Hirotaka , Abe Yasuyuki , Miyamoto Akihiro , Nishihara Masamichi , Takafuji Makoto , Ono Masao , Okayasu Satoru , Mashimo Tsutomu
Published: January 2008

The molecular-graded structures have been realized through direct copolymerization of halogenated styrene and 2-ethylhexyl methacrylate under ultra-strong gravitational field. The graded structures were clearly confirmed by EPMA and NMR spectroscopy.
Improved polymerase ribozyme efficiency on hydrophobic assemblies
Authors: Müller Ulrich F. , Bartel David P.
Published: January 2008

During an early step in the evolution of life, RNA served both as genome and as catalyst, according to the RNA world hypothesis. For self-replication, the RNA organisms must have contained an RNA that catalyzes RNA polymerization. As a first step toward recapitulating an RNA world in the laboratory, a polymerase ribozyme was generated previously by in vitro evolution and design. However, the efficiency of this ribozyme is about 100-fold too low for self-replication because of a low affinity of the ribozyme to its primer/template substrate. To improve the substrate interactions by colocalizing ribozyme and substrate on micelles, we attached hydrophobic anchors to both RNAs. We show here that the hydrophobic anchors led to aggregates with the expected size of the corresponding micelles. The micelle formation increased the polymerization yield of full-length products by 3- to 20-fold, depending on substrates and reaction conditions. With the best-characterized substrate, the improvement in polymerization efficiency was primarily due to reduced sequence-specific stalling on partially extended substrates. We discuss how, during the origin of life, micellar ribozyme aggregates could have acted as precursors to membrane-encapsulated life forms.
Proximity of the poly(A)-binding protein to a premature termination codon inhibits mammalian nonsense-mediated mRNA decay
Authors: Silva Ana Luísa , Ribeiro Patrícia , Inácio Ângela , Liebhaber Stephen A. , Romão Luísa
Published: January 2008

mRNA surveillance pathways selectively clear defective mRNAs from the cell. As such, these pathways serve as important modifiers of genetic disorders. Nonsense-mediated decay (NMD), the most intensively studied surveillance pathway, recognizes mRNAs with premature termination codons (PTCs). In mammalian systems the location of a PTC more than 50 nucleotides 5′ to the terminal exon–exon junction is a critical determinant of NMD. However, mRNAs with nonsense codons that fulfill this requirement but are located very early in the open reading frame can effectively evade NMD. The unexpected resistance of such mRNAs with AUG-proximal PTCs to accelerated decay suggests that important determinants of NMD remain to be identified. Here, we report that an NMD-sensitive mRNA can be stabilized by artificially tethering the cytoplasmic poly(A) binding protein 1, PABPC1, at a PTC-proximal position. Remarkably, the data further suggest that NMD of an mRNA with an AUG-proximal PTC can also be repressed by PABPC1, which might be brought into proximity with the PTC during cap-dependent translation and 43S scanning. These results reveal a novel parameter of NMD in mammalian cells that can account for the stability of mRNAs with AUG-proximal PTCs. These findings serve to expand current mechanistic models of NMD and mRNA translation.
Women's and men's perceptions of infertility and their associations with psychological adjustment: A dyadic approach
Authors: Benyamini Yael , Gozlan Miri , Kokia Ehud
Published: January 2008

Objectives. Research on illness perceptions and their associations with psychological adjustment to medical conditions has mostly focused on individuals coping with chronic diseases. The objective of the current study was to expand this research to the study of couples by examining the perceptions of infertility among couples undergoing treatment and their associations with each partner's psychological adjustment.

Design. The study was cross‐sectional and included two samples that differed in the stage of treatment: Sample 1 included 72 couples at their first visit to an infertility clinic and Sample 2 included 49 couples at various stages of treatment.

Methods. Participants filled in the Illness Perception Questionnaire regarding the timeline, consequences and controllability of their fertility problem and Infertility‐Specific Distress and Well‐being Scales. Dyadic analyses were conducted on the basis of the Actor–Partner Interdependence Model (APIM).

Results. The partners differed in their perceptions of infertility and their distress. Partners' psychological adjustment was related to their perceptions of the fertility problem. Among couples at their first visit, perceptions of consequences of both partners were additively related to their distress whereas controllability perceptions interacted in their association with women's distress: Highest distress was reported by women who perceived low controllability whereas their partner perceived high controllability, compared with couples who reported similar (high or low) levels of controllability.

Conclusions. A dyadic approach to studying illness perceptions can uncover patterns of couples at risk for poor adjustment. This is especially needed in contexts such as infertility, where both partners are involved and affected by the health threat.
Ambiguous women: Debates within American evangelical feminism
Authors: Sowinska Alicja
Published: February 2008

This article is an analysis of major debates within American evangelical feminism since its emergence in early 1970s. It examines ways in which American evangelical feminists negotiate their identity in the daily struggle between the mundane and the sacred, home setting and church practice,
and their private and public lives. Through presentation of personal stories and lived experiences it argues that evangelical feminists' ambiguity is a significant and powerful force that not only forges distinctive self-awareness among evangelical feminists, but also shapes diverse understandings
of evangelical feminism and shifts the boundaries of both evangelicalism and feminism in America.

Do I contradict myself?

Very well then I contradict myself, (I am large, I contain multitudes.) Walt Whitman, Song of Myself (1855) 
BHLHB2 ControlsBdnfPromoter 4 Activity and Neuronal Excitability
Authors: Jiang Xueying , Tian Feng , Du Yang , Copeland Neal G. , Jenkins Nancy A. , Tessarollo Lino , Wu Xuan , Pan Hongna , Hu Xian-Zhang , Xu Ke , Kenney Heather , Egan Sean E. , Turley Helen , Harris Adrian L. , Marini Ann M. , Lipsky Robert H.
Published: January 2008

Brain-derived neurotrophic factor (BDNF), via activation of TrkB receptors, mediates vital physiological functions in the brain, ranging from neuronal survival to synaptic plasticity, and has been implicated in the pathophysiology of neurodegenerative disorders. Although transcriptional regulation of the BDNF gene (Bdnf) has been extensively studied, much remains to be understood. We discovered a sequence withinBdnfpromoter 4 that binds the basic helix-loop-helix protein BHLHB2 and is a target for BHLHB2-mediated transcriptional repression. NMDA receptor activation de-repressed promoter 4-mediated transcription and correlated with reduced occupancy of the promoter by BHLHB2 in cultured hippocampal neurons.Bhlhb2gene −/− mice showed increased hippocampal exon 4-specificBdnfmRNA levels compared with +/+ littermates under basal and activity-dependent conditions.Bhlhb2knock-out mice also showed increased status epilepticus susceptibility, suggesting that BHLHB2 alters neuronal excitability. Together, these results support a role for BHLHB2 as a new modulator ofBdnftranscription and neuronal excitability.
Gamma Oscillations and Spontaneous Network Activity in the Hippocampus Are Highly Sensitive to Decreases in pO2and Concomitant Changes in Mitochondrial Redox State
Authors: Huchzermeyer Christine , Albus Klaus , Gabriel Hans-Jürgen , Otáhal Jakub , Taubenberger Nando , Heinemann Uwe , Kovács Richard , Kann Oliver
Published: January 2008

Gamma oscillations have been implicated in higher cognitive processes and might critically depend on proper mitochondrial function. Using electrophysiology, oxygen sensor microelectrode, and imaging techniques, we investigated the interactions of neuronal activity, interstitial pO2, and mitochondrial redox state [NAD(P)H and FAD (flavin adenine dinucleotide) fluorescence] in the CA3 subfield of organotypic hippocampal slice cultures. We find that gamma oscillations and spontaneous network activity decrease significantly at pO2levels that do not affect neuronal population responses as elicited by moderate electrical stimuli. Moreover, pO2and mitochondrial redox states are tightly coupled, and electrical stimuli reveal transient alterations of redox responses when pO2decreases within the normoxic range. Finally, evoked redox responses are distinct in somatic and synaptic neuronal compartments and show different sensitivity to changes in pO2. We conclude that the threshold of interstitial pO2for robust CA3 network activities and required mitochondrial function is clearly above the “critical” value, which causes spreading depression as a result of generalized energy failure. Our study highlights the importance of a functional understanding of mitochondria and their implications on activities of individual neurons and neuronal networks.
Avaliação otoneurológica em crianças com queixa de dificuldades escolares: pesquisa da função vestibular
Authors: Franco Eloisa Sartori , Panhoca Ivone
Published: January 2008

Segundo a literatura, a disfunção vestibular infantil pode afetar consideravelmente a habilidade de comunicação e o desempenho escolar. OBJETIVO: Estudar a função vestibular em crianças com dificuldades escolares e suas queixas vestibulares. ESTUDO DE CASO: Estudo Clínico com coorte transversal. MATERIAL E MÉTODOS: Foram estudadas 50 crianças entre 7 e 12 anos, que freqüentavam escolas públicas de Piracicaba durante os anos de 2004 e 2005. Os procedimentos foram: anamnese; exame otorrinolaringológico; exame audiológico e avaliação vestibular. RESULTADOS: Das crianças avaliadas, 62,0% não relataram dificuldades escolares e 38,0% referiram ter dificuldades. A queixa geral mais comum foi de tontura (36,0%), e o sintoma mais comum no ambiente escolar foi de cefaléia (50,0%). Encontramos 74,2% de exame vestibular normal nas crianças sem dificuldades escolares e 31,6% de normalidade nas crianças com dificuldades. Encontramos alterações vestibulares de origem periférica irritativa tanto unilateral como bilateral, num total de 68,4% para as crianças com dificuldades escolares e um total de 25,8% para crianças sem dificuldades escolares. CONCLUSÃO: A queixa de atordoamento, o sintoma de náuseas e as dificuldades em ler e copiar apresentaram uma relação estatisticamente significante. Todas as alterações vestibulares encontradas foram de origem periférica irritativa. Os dados revelaram uma relação estatisticamente significante.
A medicalização como estratégia biopolítica: um estudo sobre o consumo de psicofármacos no contexto de um pequeno município do Rio Grande do Sul
Authors: Ignácio Vivian Tatiana Galvão , Nardi Henrique Caetano
Published: January 2008

Este estudo teve como objetivo compreender como o consumo de psicofármacos se legitimou como uma tecnologia de si no interior do dispositivo de medicalização. Concluímos que esta é uma tecnologia que incide sobre os corpos por estar acoplada aos modos de subjetivação contemporâneos. A análise aqui apresentada trata do contexto social de Boa Vista das Missões, um pequeno município do Rio Grande do Sul. Realizamos uma pesquisa de campo com seis meses de duração e entrevistamos uma amostra de 400 pessoas. A análise dos relatos e das informações construídas buscou dar visibilidade aos enunciados presentes nas formações discursivas e que definem e explicam o consumo de psicofármacos por 53% da população da cidade. Utilizamos a perspectiva genealógica de Michel Foucault para refletir sobre este campo de pesquisa e problematizar a produção de modos de vida marcados por formas de controle individualizantes e totalizantes ao mesmo tempo. Neste sentido, partimos do histórico da inserção dos psicofármacos em nossa cultura para entender as dimensões que ocupam neste contexto. A análise identificou as redes enunciativas no interior do dispositivo de medicalização que fundamentam uma apresentação do biopoder que se sustenta no tripé "dependência, assistencialismo, individualismo".
Intercomparação entre quatro métodos de estimativa da altura da camada limite convectiva durante o experimento RaCCI - LBA (2002) em Rondônia - Amazônia
Authors: Santos Luiz André R. dos , Fisch Gilberto
Published: January 2008

Este trabalho tem como objetivo fazer uma comparação entre quatro diferentes métodos de estimativa da altura da Camada Limite Convectiva (CLC), utilizando dados obtidos pelo equipamento SODAR e por radiossondas, durante a campanha DRY - to - WET do experimento RaCCI - LBA (2002) em Rondônia. Os quatro métodos de estimativa utilizados foram os seguintes: o das Parcelas; do Número de Richardson; dos Perfis; e um método de medição direta através do SODAR. Os resultados mostraram que o Método das Parcelas superestimou as alturas da CLC (em 15% para às 08:00 HL e 14:00 HL e 30% nos demais horários), em quase todos os casos analisados, obtendo índices baixos do coeficiente de determinação (r²), quando comparado com os outros métodos. O Método do Número de Richardon e o Método dos Perfis apresentaram alturas muito semelhantes, com diferenças médias de menos de 50 m, alcançando um valor de r² igual a 0,97, durante o período de início da estação chuvosa. As medidas realizadas com o SODAR não se mostraram adequadas nas primeiras horas da manhã, indicando que o equipamento mediu a Camada Limite Residual (do dia anterior) e não a Camada Limite Convectiva rasa, em fase de desenvolvimento.