bluuebunny/crossref_metadata_2025 huggingface dataset:
A generalized renormalization group turbulence model and its application to a light-duty diesel engine operating in a low-temperature combustion regime
Authors: Wang Bao-Lin , Lee Chang-Wook , Reitz Rolf D , Miles Paul C , Han Zhiyu
Published: October 2012

A generalized renormalization group closure model based on the “dimensionality” of the flow strain rate is proposed and applied to engine flows in this study. In the model, the model coefficients C1, C2, and C3 are constructed as functions of the flow strain rate. Computations were made for compressing/expanding flows in a diesel engine under motoring conditions. It was found that the generalized renormalization group model performs better than the standard renormalization group k−ε model in terms of its predictions of turbulent kinetic energy and model length scales. Computations in a diesel engine operating under low-temperature combustion conditions were also investigated to further assess the performance of the present model. Predictions of the spatial distributions of unburned hydrocarbons were significantly improved and agreed well with available experimental images. Engine-out unburned hydrocarbon emission was predicted to be smaller with the generalized renormalization group model than with the standard renormalization group k−ε model.
An iterative process for verification of a meteorological data server
Authors: Thoman David , Henley Elizabeth Raley , O’Kula Kevin , Davis Frederick , Morris James
Published: October 2012

Key aspects of the verification performed on US Army Dugway Proving Ground (DPG) WeatherServer (WXS) are described. WXS is a Test and Training Enabling Architecture (TENA)-based modeling and simulation that distributes three-dimensional meteorological data over time to participants in a distributed test event or joint exercise environment. The verification features an iterative process as an effective measure to reduce time and costs while still allowing a comprehensive review. In addition, the unique role that WXS serves in efficiently providing real-time meteorological data to support Test and Evaluation (T&E) exercises is discussed.

The verification process demonstrated the fidelity of the WXS output and the correctness of the coded technical algorithms (e.g., altitude-to-pressure conversions). The iterative process involved cycles of testing and improved software builds that continued until a build of WXS was developed that functioned as designed. Insights obtained during the iterative process applied to the WXS verification included realizing the full benefits of (1) periodic communications and issue resolution among the developer, verification team, and sponsor; (2) allocating sufficient budget for the software developer’s time to support the verification process; and (3) strategically customizing the verification process to allow for an efficient testing and review process following applicable standards.
Manipulation of innate immunity by a bacterial secreted peptide: Lantibiotic nisin Z is selectively immunomodulatory
Authors: Kindrachuk Jason , Jenssen Håvard , Elliott Melissa , Nijnik Anastasia , Magrangeas-Janot Laure , Pasupuleti Mukesh , Thorson Lisa , Ma Shuhua , Easton Donna M , Bains Manjeet , Finlay Brett , Breukink Eefjan J , Georg-Sahl Hans , Hancock Robert EW
Published: October 2012

Innate immunity is triggered by a variety of bacterial molecules, resulting in both protective and potentially harmful pro-inflammatory responses. Further, innate immunity also provides a mechanism for the maintenance of homeostasis between the host immune system and symbiotic or non-pathogenic microorganisms. However, the bacterial factors that mediate these protective effects have been incompletely defined. Here, it was demonstrated that the lantiobiotic nisin Z is able to modulate host immune responses and mediate protective host immunity. Nisin Z induced the secretion of the chemokines MCP-1, IL-8 and Gro-α, and significantly reduced TNF-α induction in response to bacterial LPS in human PBMC. The results correlated with the ability of nisin Z to confer protection against both the Gram-positive organism Staphylococcus aureus, and the Gram-negatives Salmonella enterica sv. Typhimurium and Escherichia coli in murine challenge models. Mechanistic studies revealed that nisin Z modulates host immunity through similar mechanisms as natural host defense peptides, engaging multiple signal transduction pathways and growth factor receptors. The results presented herein demonstrate that, in addition to nisin Z, other bacterial cationic peptides and, in particular, the lantibiotics, could represent a new class of secreted bacterial molecule with immunomodulatory activities.
Clozapine treatment of patients with refractory schizophrenia, concurrent dengue infection and hematological abnormalities: three case reports
Authors: Nunes Emerson Arcoverde , Rezende Tatiana M.N. , Morais Silvio L. , Crippa José A.S. , Dursun Serdar M. , Baker Glen B. , Hallak Jaime E.C.
Published: October 2012

Background:

Dengue is a febrile illness that is most common in tropical areas but is recognized worldwide as one of the most important arbovirus diseases of humans. This febrile illness generally has a course with mild alterations in white blood cell count, but there are also rare cases of severe neutropenia or agranulocytosis during dengue infection. Clozapine (CLZ) remains the most effective treatment for schizophrenia, but because of its poor side effect profile, in particular due to the increased risk of neutropenia and agranulocytosis, it is generally used for patients whose condition responds poorly to other antipsychotics.

Methods:

We report three cases of dengue infection in patients with refractory schizophrenia who were using CLZ, and we discuss the implications of this infection on the continuation of CLZ treatment in these patients.

Results:

Of these three cases with dengue infection and co-occurence of CLZ use, the first would be classified as severe neutropenia and the second as moderate leucopenia; the last case had a white blood cell (WBC) count inside the normal range, and had no need to change his antipsychotic. The first and the second patient presented a worsening in their schizophrenic psychopathologies, after CLZ withdrawal, evolving into catatonic states, that were reverted after the careful reintroduction of CLZ.

Discussion:

It is very likely that during dengue epidemics many patients with schizophrenia and using CLZ have their treatment permanently discontinued given WBC count concerns, causing relapse of symptoms of schizophrenia and impairment of quality of life of these patients.This is the first report of neutropenia cases among CLZ-treated patients during dengue infection that describes the withdrawal of CLZ and its successful readministration.
Rate of workhardening influencing subzero temperature tensile strength properties of heat treated aluminium alloy 7010 plates
Authors: Mukhopadhyay A K , Prasad K S , Murali D S K
Published: October 2012

The tensile properties of aluminium alloy 7010 plates, heat treated to varying aging conditions, i.e. naturally aged, underaged, peak aged and overaged, were examined at ambient and subzero (−50°C) temperatures. It is shown that the maximum increase in strength properties (both 0·2 proof stress and ultimate tensile strength) upon changing the test temperature from ambient to subzero (i.e. −50°C) is obtained in the case of the naturally aged samples, while there is a minimal increase in the strength properties of the underaged samples when tested at −50°C. These results are discussed in light of changes in the workhardening behaviour of the materials with aging.
Effect of alumina particle size and thermal condition of casting on microstructure and mechanical properties of stir cast Al–Al2O3 composites
Authors: Sarmasti A B , Yazdanirad M , Nouri Khezrabad M , Karbalaie M
Published: October 2012

Metal matrix composites are considered as a distinct category of the advanced materials, which have low weight, high strength, high modulus of elasticity, low thermal expansion coefficient and high wear resistance. Among them, Al–Al2O3 composites have achieved significant attention due to their desired properties. In the present research, Al–Al2O3 composites with 5 vol.- alumina were produced by stir casting at a temperature of 800°C. Two different particle sizes of alumina were used as 53–63 and 90–105 μm. The microstructure of the samples was evaluated by SEM. In addition, the mechanical properties of the samples were measured, and hence, the optimum temperature and particle size of alumina to be added to the Al matrix were determined. The results demonstrated the positive effect of alumina on improving the properties of Al–Al2O3 composites.
Heat transfer during solidification of chemically modified Al–Si alloys around a copper chill
Authors: Prabhu K N , Hegde S
Published: October 2012

The solidifying metal/chill contour will significantly affect the boundary heat transfer coefficients, and solidification modellers should be aware of the casting conditions for which the heat transfer coefficients are determined. The previous work carried out on solidification of Al–Si alloys in a metallic mould and solidification against bottom/top chills has shown that modification and chilling have synergetic effect resulting in a significant increase in the heat flux transients at the casting/chill interface. In the present work, the heat transfer during solidification of unmodified and chemically modified Al–Si alloys around a cylindrical copper chill was investigated. Heat flux transients were estimated using lumped heat capacitance method. Lower peak heat flux was obtained with chemically modified alloy. This is in contrast to the results reported for alloys solidifying against chills and in metallic moulds. The chill thermal behaviour and heat transfer to the chill material when surrounded by modified and unmodified alloys were explained on the basis of the decrease in the degree of undercooling in the case of modified alloy as compared to unmodified alloy and the change in contact condition and shrinkage characteristics of the alloy due to the addition of chemical modifiers.
Cast joining of cast iron to aluminium casting matrix
Authors: Moosavi-Khoonsari E , Jalilian F , Paray F , Emadi D , Drew R A L
Published: October 2012

The present study focused on reinforcing Al–Si–Cu alloy with a cast iron insert and using Zn– xAl–3Si–0·5Mg (wt-) intermediate alloys by the cast joining technique to take advantage of lightness and stiffness of the hybrid structure. The experimental set-up consisted of coating the insert using hot dipping method followed by immersing the coated insert into the Al melt and allowing the system to cool down to the room temperature. The quality of Al–Fe joints in terms of morphology, thickness, chemistry and microhardness was evaluated as a function of coating composition and immersion time in the Al melt. Characteristics of reaction layer at the coating/insert interface and its effects on the joint properties were determined using microstructural analysis and thermodynamic calculations. Combination of a suitable coating containing 27 wt-Al and optimised process parameters, including 1 min immersion time, resulted in the formation of an Al–Fe joint with promising characteristics.
Acute toxicities of unrelated bone marrow versus peripheral blood stem cell donation: results of a prospective trial from the National Marrow Donor Program
Authors: Pulsipher Michael A. , Chitphakdithai Pintip , Logan Brent R. , Shaw Bronwen E. , Wingard John R. , Lazarus Hillard M. , Waller Edmund K. , Seftel Matthew , Stroncek David F. , Lopez Angela M. , Maharaj Dipnarine , Hematti Peiman , O'Donnell Paul V. , Loren Alison W. , Leitman Susan F. , Anderlini Paolo , Goldstein Steven C. , Levine John E. , Navarro Willis H. , Miller John P. , Confer Dennis L.
Published: October 2012

Although peripheral blood stem cells (PBSCs) have replaced bone marrow (BM) as the most common unrelated donor progenitor cell product collected, a direct comparison of concurrent PBSC versus BM donation experiences has not been performed. We report a prospective study of 2726 BM and 6768 PBSC donors who underwent collection from 2004 to 2009. Pain and toxicities were assessed at baseline, during G-CSF administration, on the day of collection, within 48 hours of donation, and weekly until full recovery. Peak levels of pain and toxicities did not differ between the 2 donation processes for most donors. Among obese donors, PBSC donors were at increased risk of grade 2 to 4 pain as well as grade 2 to 4 toxicities during the pericollection period. In contrast, BM donors were more likely to experience grade 2 to 4 toxicities at 1 week and pain at 1 week and 1 month after the procedure. BM donors experienced slower recovery, with 3% still not fully recovered at 24 weeks, whereas 100% of PBSC donors had recovered. Other factors associated with toxicity included obesity, increasing age, and female sex. In summary, this study provides extensive detail regarding individualized risk patterns of PBSC versus BM donation toxicity, suggesting donor profiles that can be targeted with interventions to minimize toxicity.
Understanding the role of scientific evidence in consumer evaluation of natural health products for osteoarthritis an application of the means end chain approach
Authors: Tsui Teresa , Boon Heather , Boecker Andreas , Kachan Natasha , Krahn Murray
Published: October 2012

Background

Over 30% of individuals use natural health products (NHPs) for osteoarthritis-related pain. The Deficit Model for the Public Understanding of Science suggests that if individuals are given more information (especially about scientific evidence) they will make better health-related decisions. In contrast, the Contextual Model argues that scientific evidence is one of many factors that explain how consumers make health-related decisions. The primary objective was to investigate how the level of scientific evidence supporting the efficacy of NHPs impacts consumer decision-making in the self-selection of NHPs by individuals with osteoarthritis.

Methods

The means-end chain approach to product evaluation was used to compare laddering interviews with two groups of community-dwelling Canadian seniors who had used NHPs to treat their osteoarthritis. Group 1 (n=13) had used only NHPs (glucosamine and/or chondroitin) with “high” scientific evidence of efficacy. Group 2 (n=12) had used NHPs (methylsulfonylmethane (MSM) and/or bromelain) with little or no scientific evidence supporting efficacy. Content analysis and generation of hierarchical value maps facilitated the identification of similarities and differences between the two groups.

Results

The dominant decision-making chains for participants in the two scientific evidence categories were similar. Scientific evidence was an important decision-making factor but not as important as the advice from health care providers, friends and family. Most participants learned about scientific evidence via indirect sources from health care providers and the media.

Conclusions

The Contextual Model of the public understanding of science helps to explain why our participants believed scientific evidence is not the most important factor in their decision to use NHPs to help manage their osteoarthritis.
The importance of the macrophage within the human endometrium
Authors: Thiruchelvam Uma , Dransfield Ian , Saunders Philippa T K , Critchley Hilary O D
Published: October 2012

Review on the regulation, phenotype, and role of the macrophage within the endometrium during the menstrual cycle.

The human endometrium is exposed to cyclical fluctuations of ovarian-derived sex steroids resulting in proliferation, differentiation (decidualization), and menstruation. An influx of leukocytes (up to 15% macrophages) occurs during the latter stages of the menstrual cycle, including menses. We believe the endometrial macrophage is likely to play an important role during the menstrual cycle, especially in the context of tissue degradation (menstruation), which requires regulated repair, regeneration, and phagocytic clearance of endometrial tissue debris to re-establish tissue integrity in preparation for fertility. The phenotype and regulation of the macrophage within the endometrium during the menstrual cycle and interactions with other cell types that constitute the endometrium are currently unknown and are important areas of study. Understanding the many roles of the endometrial macrophage is crucial to our body of knowledge concerning functionality of the endometrium as well as to our understanding of disorders of the menstrual cycle, which have major impacts on the health and well-being of women.
Initial Molecular Response at 3 Months May Predict Both Response and Event-Free Survival at 24 Months in Imatinib-Resistant or -Intolerant Patients With Philadelphia Chromosome–Positive Chronic Myeloid Leukemia in Chronic Phase Treated With Nilotinib
Authors: Branford Susan , Kim Dong-Wook , Soverini Simona , Haque Ariful , Shou Yaping , Woodman Richard C. , Kantarjian Hagop M. , Martinelli Giovanni , Radich Jerald P. , Saglio Giuseppe , Hochhaus Andreas , Hughes Timothy P. , Müller Martin C.
Published: October 2012

Purpose

The association between initial molecular response and longer-term outcomes with nilotinib was examined.

Patients and Methods

Patients with imatinib-resistant or -intolerant chronic myeloid leukemia in chronic phase from the phase II nilotinib registration study with available postbaseline BCR-ABL1 transcript assessments were included (N = 237).

Results

BCR-ABL1 transcript levels (International Scale [IS]) at 3 months correlated with complete cytogenetic response (CCyR) by 24 months. Patients with BCR-ABL1 (IS) of > 1% to ≤ 10% at 3 months with nilotinib had higher cumulative incidence of CCyR by 24 months than patients with BCR-ABL1 (IS) of > 10% (53% v 16%). BCR-ABL1 (IS) at 3 months predicted major molecular response (MMR) by 24 months. Cumulative incidence of MMR by 24 months for patients with BCR-ABL1 (IS) of > 0.1% to ≤ 1%, > 1% to ≤ 10%, and > 10% was 65%, 27%, and 9%, respectively. These differences were observed for patients with or without baseline BCR–ABL1 mutations and for those with imatinib resistance or intolerance. Estimated event-free survival (EFS) rates at 24 months decreased with higher transcript levels at 3 months; patients with BCR-ABL1 (IS) of ≤ 1% had an estimated 24-month EFS rate of 82%, compared with 70% for patients with BCR-ABL1 (IS) of > 1% to ≤ 10% and 48% for patients with BCR-ABL1 (IS) of > 10%.

Conclusion

Patients with BCR-ABL1 (IS) of > 10% at 3 months had a lower cumulative incidence of CCyR and MMR and lower rates of EFS versus patients with BCR-ABL1 (IS) of ≤ 10%. Prospective studies may determine whether close monitoring or alternative therapies are warranted for patients with minimal initial molecular response.
Impact of [18F]Fluorodeoxyglucose Positron Emission Tomography Response Evaluation in Patients With High–Tumor Burden Follicular Lymphoma Treated With Immunochemotherapy: A Prospective Study From the Groupe d'Etudes des Lymphomes de l'Adulte and GOELAMS
Authors: Dupuis Jehan , Berriolo-Riedinger Alina , Julian Anne , Brice Pauline , Tychyj-Pinel Christelle , Tilly Hervé , Mounier Nicolas , Gallamini Andrea , Feugier Pierre , Soubeyran Pierre , Colombat Philippe , Laurent Guy , Berenger Nathalie , Casasnovas Rene-Olivier , Vera Pierre , Paone Gaetano , Xerri Luc , Salles Gilles , Haioun Corinne , Meignan Michel
Published: October 2012

Purpose

[18F]Fluorodeoxyglucose positron emission tomography (PET) is widely used for the staging and restaging of patients with aggressive lymphoma, but less is known about the utility of PET in patients with follicular lymphoma (FL). In a prospective study, we evaluated the prognostic value of PET performed during treatment and at the end of treatment in 121 patients with FL treated with first-line immunochemotherapy.

Patients and Methods

Patients with previously untreated high–tumor burden FL were treated with six cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) plus two cycles of rituximab, without rituximab maintenance. PET was performed before treatment, after four cycles of R-CHOP (interim PET), and at the end of treatment (final PET). PET scans were centrally reviewed.

Results

The total number of patients included was 121. Median age was 57 years. After central review, interim PET (n = 111) was negative in 76% of patients, and final PET (n = 106) was negative in 78%. With a median follow-up of 23 months, 2-year progression-free survival rates were 86% for interim PET–negative versus 61% for interim PET–positive patients (P = .0046) and 87% for final PET–negative versus 51% for final PET–positive patients (P < .001), respectively. Two-year overall survival also significantly differed according to final PET results: 100% versus 88% (P = .0128).

Conclusion

PET performed either after four cycles of R-CHOP or at the end of therapy was strongly predictive of outcome in this prospective study. Therapeutic intervention based on PET results during or after inductive treatment should be evaluated.
Results From a Prospective, Open-Label, Phase II Trial of Bendamustine in Refractory or Relapsed T-Cell Lymphomas: The BENTLY Trial
Authors: Damaj Gandhi , Gressin Rémy , Bouabdallah Krimo , Cartron Guillaume , Choufi Bachra , Gyan Emmanuel , Banos Anne , Jaccard Arnaud , Park Sophie , Tournilhac Olivier , Schiano-de Collela Jean-Marc , Voillat Laurent , Joly Bertrand , Le Gouill Steven , Saad Alain , Cony-Makhoul Pascale , Vilque Jean-Pierre , Sanhes Laurence , Schmidt-Tanguy Aline , Bubenheim Michael , Houot Roch , Diouf Momar , Marolleau Jean-Pierre , Béné Marie-Christine , Martin Antoine , Lamy Thierry
Published: October 2012

Purpose

To determine the efficacy and safety of bendamustine as a single agent in refractory or relapsed T-cell lymphomas.

Patients and Methods

Patients with histologically confirmed peripheral T-cell lymphoma (PTCL) or cutaneous T-cell lymphoma who progressed after one or more lines of prior chemotherapy received bendamustine at 120 mg/m2 per day on days 1 through 2 every 3 weeks for six cycles. The primary end point was overall response rate (ORR). Secondary end points were duration of response (DOR), progression-free survival (PFS), and overall survival (OS).

Results

Of the 60 patients included, 27 (45%) were refractory to their last prior chemotherapy, and the median duration of the best previous response was 6.6 months. Histology was predominantly angioimmunoblastic lymphadenopathy and PTCL not otherwise specified. The disease was disseminated in the majority of patients (87%). The median number of previous lines of chemotherapy was one (range, one to three). Twenty patients (33%) received fewer than three cycles of bendamustine, mostly because of disease progression. In the intent-to-treat population, the ORR was 50%, including complete response in 17 patients (28%) and partial response in 13 patients (22%). Bendamustine showed consistent efficacy independent of major disease characteristics. The median values for DoR, PFS, and OS were 3.5, 3.6, and 6.2 months, respectively. The most frequent grade 3 to 4 adverse events were neutropenia (30%), thrombocytopenia (24%), and infections (20%).

Conclusion

Bendamustine showed an encouraging high response rate across the two major PTCL subtypes, independent of age and prior treatment, with acceptable toxicity in refractory or relapsed T-cell lymphoma.
Impact of Azacitidine Before Allogeneic Stem-Cell Transplantation for Myelodysplastic Syndromes: A Study by the Société Française de Greffe de Moelle et de Thérapie-Cellulaire and the Groupe-Francophone des Myélodysplasies
Authors: Damaj Gandhi , Duhamel Alain , Robin Marie , Beguin Yves , Michallet Mauricette , Mohty Mohamad , Vigouroux Stephane , Bories Pierre , Garnier Alice , El Cheikh Jean , Bulabois Claude-Eric , Huynh Anne , Bay Jacques-Olivier , Legrand Faeyzeh , Deconinck Eric , Fegueux Nathalie , Clement Laurence , Dauriac Charles , Maillard Natacha , Cornillon Jérôme , Ades Lionel , Guillerm Gaelle , Schmidt-Tanguy Aline , Marjanovic Zora , Park Sophie , Rubio Marie-Thérèse , Marolleau Jean-Pierre , Garnier Federico , Fenaux ierre , Yakoub-Agha Ibrahim
Published: October 2012

Purpose

To investigate the impact of prior-to-transplantation azacitidine (AZA) on patient outcome after allogeneic stem-cell transplantation (alloSCT) for myelodysplastic syndrome (MDS).

Patients and Methods

Of the 265 consecutive patients who underwent alloSCT for MDS between October 2005 and December 2009, 163 had received cytoreductive treatment prior to transplantation, including induction chemotherapy (ICT) alone (ICT group; n = 98), AZA alone (AZA group; n = 48), or AZA preceded or followed by ICT (AZA-ICT group; n = 17). At diagnosis, 126 patients (77%) had an excess of marrow blasts, and 95 patients (58%) had intermediate-2 or high-risk MDS according to the International Prognostic Scoring System (IPSS). Progression to more advanced disease before alloSCT was recorded in 67 patients. Donors were sibling (n = 75) or HLA-matched unrelated (10/10; n = 88). They received blood (n = 142) or marrow (n = 21) grafts following either myeloablative (n = 33) or reduced intensity (n = 130) conditioning.

Results

With a median follow-up of 38.7 months, 3-year outcomes in the AZA, ICT, and AZA-ICT groups were 55%, 48%, and 32% (P = .07) for overall survival (OS); 42%, 44%, and 29% (P = .14) for event-free survival (EFS); 40%, 37%, and 36% (P = .86) for relapse; and 19%, 20%, and 35% (P = .24) for nonrelapse mortality (NRM), respectively. Multivariate analysis confirmed the absence of statistical differences between the AZA and the ICT groups in terms of OS, EFS, relapse, and NRM.

Conclusion

With the goal of downstaging underlying disease before alloSCT, AZA alone led to outcomes similar to those for standard ICT.
Recommendations for the Return of Research Results to Study Participants and Guardians: A Report From the Children's Oncology Group
Authors: Fernandez Conrad V. , Ruccione Kathleen , Wells Robert J. , Long Jay B. , Pelletier Wendy , Hooke Mary C. , Pentz Rebecca D. , Noll Robert B. , Baker Justin N. , O'Leary Maura , Reaman Gregory , Adamson Peter C. , Joffe Steven
Published: October 2012

Purpose

The Children's Oncology Group (COG) strongly supports the widely recognized principle that research participants should be offered a summary of study results. The mechanism by which to do so in a cooperative research group setting has not been previously described.

Methods

On the basis of a review of the available empirical and theoretic literature and on iterative, multidisciplinary discussion, a COG Return of Results Task Force (RRTF) offered detailed recommendations for the return of results to research study participants.

Results

The RRTF established guidelines for the notification of research participants and/or their parents/guardians about the availability of research results, a mechanism for and timing of sharing results via registration on the COG public Web site, the scope of the research to be shared, the target audience, and a process for creating and vetting lay summaries of study results. The RRTF recognized the challenges in adequately conveying complex scientific results to audiences with varying levels of health literacy and recommended that particularly sensitive or complex results be returned using direct personal contact. The RRTF also recommended evaluation of the cost, effectiveness, and impact of sharing results.

Conclusion

These recommendations provide a framework for the offering and returning of results to participants. They can be used by individual investigators, multi-investigator research collaboratives, and large cooperative groups.
Fission yeast TORC1 prevents eIF2α phosphorylation in response to nitrogen and amino acids via Gcn2 kinase
Authors: Valbuena Noelia , Rozalén Ana Elisa , Moreno Sergio
Published: October 2012

Serine 51 phosphorylation of the eukaryotic initiation factor-2α (eIF2α) is an important mechanism involved in blocking general protein synthesis in response to diverse types of stress. In fission yeast, three kinases (Hri1, Hri2 and Gcn2) can phosphorylate eIF2α at serine 51. In this study, we show that Tor2, as part of the TORC1 complex, prevents the phosphorylation of eIF2α in cells growing in the presence of nitrogen and amino acids. Inhibition of TORC1, either by rapamycin treatment, mutation of Tor2 or nitrogen deprivation, induces Gcn2-dependent phosphorylation of eIF2α.
Active involvement of micro-lipid droplets and lipid-droplet-associated proteins in hormone-stimulated lipolysis in adipocytes
Authors: Hashimoto Takeshi , Segawa Hiroki , Okuno Masanari , Kano Hideaki , Hamaguchi Hiro-o , Haraguchi Tokuko , Hiraoka Yasushi , Hasui Shiho , Yamaguchi Tomohiro , Hirose Fumiko , Osumi Takashi
Published: October 2012

The regulation of lipolysis in adipocytes involves coordinated actions of many lipid droplet (LD)-associated proteins such as perilipin, hormone sensitive lipase (HSL), adipose triglyceride lipase (ATGL), and its activator protein, CGI-58. Here, we describe the cellular origin and physiological significance of micro LDs (mLDs) that emerge in the cytoplasm during active lipolysis, as well as the roles of key lipolytic proteins on mLDs in differentiated 3T3-L1 adipocytes. Multiplex coherent anti-Stokes Raman scattering (CARS) microscopy demonstrated that mLDs receive the fatty acid (FA) moiety of triglyceride from pre-existing LDs during lipolysis. However, when FA re-esterification was blocked, mLDs did not emerge. Time-lapse imaging of GFP-tagged LD-associated proteins and immunocytochemical analyses showed that particulate structures carrying LD-associated proteins emerged throughout the cells upon lipolytic stimulation, but not when FA re-esterification was blocked. Overall lipolysis, as estimated by glycerol release, was significantly lowered by blocking re-esterification, whereas release of free FAs was enhanced. ATGL was co-immunoprecipitated with CGI-58 from the homogenates of lipolytically stimulated cells. Following CGI-58 knockdown or ATGL inhibition with bromoenol lactone, release of both glycerol and FA was significantly lowered. AICAR, an activator of AMP-activated protein kinase, significantly increased FA release, in accordance with increased expression of ATGL, even in the absence of CGI-58. These results suggest that, besides on the surface of pre-existing central LDs, LD-associated proteins are actively involved in lipolysis on mLDs that are formed by FA re-esterification. Regulation of mLDs and LD-associated proteins may be an attractive therapeutic target against lipid-associated metabolic diseases.
Direct mobilisation of lysosomal Ca2+ triggers complex Ca2+ signals
Authors: Kilpatrick Bethan S. , Eden Emily R. , Schapira Anthony H. , Futter Clare E. , Patel Sandip
Published: October 2012

Accumulating evidence implicates acidic organelles of the endolysosomal system as mobilisable stores of Ca2+ but their relationship to the better-characterised endoplasmic reticulum (ER) Ca2+ store remains unclear. Here we show that rapid osmotic permeabilisation of lysosomes evokes prolonged, spatiotemporally complex Ca2+ signals in primary cultured human fibroblasts. These Ca2+ signals comprised an initial response that correlated with lysosomal disruption and secondary long-lasting spatially heterogeneous Ca2+ oscillations that required ER-localised inositol trisphosphate receptors. Electron microscopy identified extensive membrane contact sites between lysosomes and the ER. Mobilisation of lysosomal Ca2+ stores is thus sufficient to evoke ER-dependent Ca2+ release probably through lysosome–ER membrane contact sites, and akin to the proposed mechanism of action of the Ca2+ mobilising messenger nicotinic acid adenine dinucleotide phosphate (NAADP). Our data identify functional and physical association of discrete Ca2+ stores important for the genesis of Ca2+ signal complexity.
A new accurate, simple formula for LDL-cholesterol estimation based on directly measured blood lipids from a large cohort
Authors: de Cordova Caio Mauricio Mendes , de Cordova Mauricio Mendes
Published: October 2012

Background

Low-density lipoprotein cholesterol (LDL-c) is the major measured parameter for cardiovascular risk assessment. The generally accepted formula (LDL-F) for estimating LDL-c developed by Friedewald and colleagues in 1972 using data from 448 individuals suffers from known inaccuracies at extremes of triglyceride (TG) and total cholesterol (TC) values.

Methods

We generated new formulas based on a large Brazilian database containing directly measured lipid values from 10,664 fasted individuals. This database LDL-c was measured by the LDL-C Select FS (DiaSys) system, a homogeneous method without centrifugation. The formulas were generated using linear and non-linear approaches, and the formula with the highest accuracy and simplicity for general clinical use was selected.

Results

The simple formula LDL-c = 3/4 (TC - HDL-c) provided an accurate estimate of LDL-c, a higher correlation with directly measured LDL (r = 0.93) compared with LDL-F (r = 0.87), and also a higher accuracy.

Conclusions

The new formula outperformed several other LDL-c formulas over a wide range of TC, HDL-c and TG values. The validation and application of this formula in other populations is warranted.
Which point-of-care creatinine analyser for radiology: direct comparison of the i-Stat and StatStrip creatinine methods with different sample types
Authors: Dimeski Goce , Tilley Vera , Jones Brock W , Brown Nigel N
Published: October 2012

Background

Availability of whole blood creatinine estimation for patients scheduled to undergo radiological contrast investigations can provide information to aid patient care by reducing adverse effects and improving departmental efficiencies.

Methods

We performed imprecision studies, different patient sample type comparison in 40 participants, and a limited interference study with dopamine and dobutamine on the i-Stat and StatStrip point-of-care enzymatic analysers with the Beckman DxC800 Jaffe assay.

Results

Imprecision results showed that the i-Stat performed better. Patient comparison data indicated that the i-Stat provided better correlation than the StatStrip for all the different sample types with correlation coefficients (r2) being 0.995-0.996 and 0.918-0.995, respectively. The i-Stat results had a small positive bias of 6-9% for the three different sample types, which required different reference intervals. The StatStrip method showed greater scatter and overall small negative bias of 26% for the whole blood samples and a 10% positive bias with the plasma samples. Dopamine caused significant positive interference with the i-Stat only while dobutamine caused a small negative bias with the StatStrip method only.

Conclusions

The findings indicated there are differences offered by the two systems. The StatStrip requires a very small finger prick capillary sample, calculates estimation of the glomerular filtration rate and has an adjustment option to improve correlation with the local method. The i-Stat offers better analytical imprecision and patient comparison with the laboratory method with the three sample types but showed significant interference from dopamine. A final consideration was the availability of middleware to capture patient results with the i-Stat. Based on all the study data, the i-Stat was recommended.
Differences in the classification of hypertensive controlled patient in primary care: Cross sectional study
Authors: Barrera Lena , Millett Christopher , Blangiardo Marta , Pape Utz J. , Majeed Azeem
Published: October 2012

Objectives

To examine differences in blood pressure control using the 2006 National Institute for Health and Clinical Excellence (NICE) guidelines and the 2007 Quality and Outcome Framework (QOF) standards.

Design

Cross-sectional study.

Setting

28 general practices located in Wandsworth, London.

Participants

Hypertensive patients aged 17 years and over.

Main outcomes measures

Percentage of hypertensive patients classified as a hypertensive controlled patient (HCP) by each standard.

Results

79.5% of patients were classified as a HCP by the QOF target and 60.7% by the NICE target. 93% and 14% of practices had more than 70% of patients classified as a HPC by using the QOF and NICE targets respectively. By applying the QOF target, men aged 45–64 years and 65 years and over had significantly higher probability of being classified as a HCP compared to those aged 17–44 years, OR 1.34 (1.08–.165) and OR 2.15 (1.61–2.87) respectively. Regardless of the target, for men the probability of being classified as a HCP increased with age.

Conclusion

Better achievement of blood pressure control targets is present when the less stringent QOF target is used. Men aged 65 years and over were more likely to be classified as a HCP. Greater consistency is needed between the clinical targets in QOF and NICE guidance.
Public Emergency Laws & Regulations: Understanding Constraints & Opportunities
Authors: Wilson Lydia R. , McCreight Robert
Published: October 2012

The thrust of this article is to provide emergency managers with a general introductory overview of major issues involved in public emergency law and review some basic issues which comprise elements of the legal framework of crisis management. This article is designed to be an informative piece for emergency managers about the law as it relates to handling a crisis event. The goal is to increase awareness of some of the major legal issues associated with a crisis regardless of magnitude and determine the extent to which this information may guide planning, preparedness and response options for the various local and state governments involved. This article, however, the authors outline a way to encourage a dialogue between emergency managers and corporate counsel, at least annually, to review legal issues and trends. The authors’ does not present legal advice. Instead, a primary goal is to clarify and illustrate some of the emergency manager’s legal duties and point out the possible risks of legal liability.
A reduction theorem for the blockwise Alperin weight conjecture
Authors: Späth Britta
Published: October 2012

We show that the blockwise version of the Alperin weight conjecture is true if for every finite non-abelian simple group a set of conditions holds. Furthermore we prove that several series of simple groups satisfy these assumptions. This refines recent work of Navarro and Tiep, who proved an analogous reduction theorem for the non-blockwise version of the Alperin weight conjecture.
Wo stehen wir in der Grammatiktheorie?
Bemerkungen anlässlich eines Buchs
von Stefan Müller
Authors: Sternefeld Wolfgang , Richter Frank
Published: October 2012

Stefan Müller’s recent introductory textbook, “Grammatiktheorie”, is an
astonishingly comprehensive and insightful survey for beginning students of
the present state of syntactic theory. Müller’s inspiring exposition of modern
grammatical reasoning, which takes into account frameworks as diverse
as Categorial Grammar, Tree Adjoining Grammar, Head-driven
Phrase Structure Grammar, Minimalism and Construction Grammar
(among others!), leads us to an exploration of the validity of the popular
claim that grammar theory provides explanations for the human ability to
acquire and use linguistic skills. To what extent this claim is justified seems
unclear in light of the recent wealth of developments in neighboring fields
such as computational linguistics, corpus linguistics, psycholinguistics, and
statistical language modeling. In the first section of the paper, we discuss
what we perceive to be a widening gap between the claims to all-embracing
explanation in theoretical linguistics and the increasingly disturbing neglect
of a vast field of new data and analyses in the above-mentioned related
disciplines. Section 2 gives a condensed survey of the contents of Müller’s
book and discusses the relationships between the various frameworks. We
conclude with sceptical remarks on the book’s preference of breadth over
depth, the legacy of traditional grammar theory, and the future perspective
of linguistics.
Genes that characterize T3-predominant Graves' thyroid tissues
Authors: Matsumoto Chisa , Ito Mitsuru , Yamada Hiroya , Yamakawa Noriko , Yoshida Hiroshi , Date Arisa , Watanabe Mikio , Hidaka Yoh , Iwatani Yoshinori , Miyauchi Akira , Takano Toru
Published: October 2012

Objective

3,5,3′-Triiodothyronine (T3)-predominant Graves' disease is characterized by the increasing volume of thyroid goiter resulting in poor prognosis. Although type 1 and type 2 iodothyronine deiodinases (DIO1andDIO2respectively) are known to be overexpressed in the thyroid tissues of T3-predominant Graves' disease, the pathogenesis of this disease is still unclear. The aim of our study is to identify genes that characterize T3-predominant Graves' disease tissue in order to clarify the molecular mechanism of this disease.

Design and methods

mRNAs from two thyroid tissues of both typical T3-predominant and common-type Graves' disease were analyzed with DNA microarrays with probes for 28 869 genes. Genes identified to be differentially expressed between the two groups were further analyzed in the second and third screenings using 70 Graves' thyroid tissues by real-time quantitative RT-PCR.

Results

Twenty-three candidate genes were selected as being differentially expressed in the first screening with microarrays. Among these, seven genes, leucine-rich repeat neuronal 1 (LRRN1), bone morphogenetic protein 8a (BMP8A), N-cadherin (CDH2), phosphodiesterase 1A (PDE1A), creatine kinase mitochondrial 2 (CKMT2), integrin beta-3 (ITGB3), and protein tyrosine phosphatase non-receptor type 4 (PTPN4), were confirmed to be differentially expressed inDIO1orDIO2over- and underexpressing Graves' tissues.

Conclusions

These genes are related to the characteristics of T3-predominant Graves' disease, such as high titer level of serum anti-TSH receptor antibody, high free T3to free thyroxine ratio, and a large goiter size. They might play a role in the pathogenesis of T3-predominant Graves' disease.
Association between menstrual cycle irregularities and endocrine and metabolic characteristics of the polycystic ovary syndrome
Authors: Panidis Dimitrios , Tziomalos Konstantinos , Chatzis Panagiotis , Papadakis Efstathios , Delkos Dimitrios , Tsourdi Elena A , Kandaraki Eleni A , Katsikis Ilias
Published: October 2012

Objective

Insulin resistance (IR) is frequent in polycystic ovary syndrome (PCOS) and contributes to the increased risk for type 2 diabetes mellitus and cardiovascular disease of this population. Several markers of IR are used but most are expensive or have limited sensitivity and specificity. Preliminary data suggest that the menstrual cycle pattern correlates with IR in PCOS but existing studies are small. We aimed to assess the relationship between the type of menstrual cycle irregularities and IR in PCOS.

Design

Prospective study.

Methods

We studied 1285 women with PCOS, divided according to the menstrual cycle pattern.

Results

Patients with isolated secondary amenorrhea and those with secondary amenorrhea alternating with regular menstrual cycles were more insulin resistant than patients with regular cycles (Group D). Patients with isolated oligomenorrhea were also more insulin resistant than Group D. However, patients with oligomenorrhea alternating with regular cycles, secondary amenorrhea, or polymenorrhea had comparable levels of markers of IR with Group D. Moreover, patients with oligomenorrhea alternating with regular cycles were less insulin resistant than patients with secondary amenorrhea alternating with regular cycles. Finally, patients with isolated polymenorrhea and those with polymenorrhea alternating with regular cycles had comparable levels of markers of IR with Group D.

Conclusions

Amenorrhea is associated with more pronounced IR in PCOS, and oligomenorrhea portends a less excessive risk for IR than amenorrhea whereas polymenorrhea appears to be even more benign metabolically. Therefore, the type of menstrual cycle abnormality appears to represent a useful tool for identifying a more adverse metabolic profile in PCOS.
Multiple follicle culture supports primary follicle growth through paracrine-acting signals
Authors: Hornick J E , Duncan F E , Shea L D , Woodruff T K
Published: October 2012

In vitro follicle growth in alginate hydrogels is a unique and versatile method for studying ovarian and follicle biology that may also have implications for fertility preservation. Current culture systems support the development of isolated mouse follicles from the secondary stage onward. However, it has been a challenge to grow smaller follicles in vitro due to the dissociation of the oocyte from companion somatic cells. Recent work has demonstrated that coculturing primary follicles with mouse embryonic fibroblasts or ovarian stromal cells supports follicle survival and growth. In this study, we demonstrate that follicles themselves can exert a beneficial coculture effect. When primary follicles were cultured in groups of five or ten (multiple follicle culture), there was increased growth and survival. The multiple follicle culture approach maintained follicle integrity and resulted in the formation of antral stage follicles containing meiotically competent gametes. The growth and survival of primary follicles were highly number dependent, with the most significant enhancement observed when the largest number of follicles was grown together. Our data suggest that the follicle unit is necessary to produce the secreted factors responsible for the supportive effects of multiple follicle culture, as neither denuded oocytes, oocyte-secreted factors, nor granulosa cells alone were sufficient to support early follicle growth in vitro. Therefore, there may be signaling from both the oocyte and the follicle that enhances growth but requires both components in a feedback mechanism. This work is consistent with current in vivo models for follicle growth and thus advances the movement to recapitulate the ovarian environment in vitro.
Relief of Pain and Anxiety in Pediatric Patients in Emergency Medical Systems
Authors: Fein Joel A. , Zempsky William T. , Cravero Joseph P. ,   THE COMMITTEE ON PEDIATRIC EMERGENCY MEDICINE AND SECTION ON ANESTHESIOLOGY AND PAIN MEDICINE
Published: October 2012

This Clinical Report was reaffirmed December 2020.

Control of pain and stress for children is a vital component of emergency medical care. Timely administration of analgesia affects the entire emergency medical experience and can have a lasting effect on a child’s and family’s reaction to current and future medical care. A systematic approach to pain management and anxiolysis, including staff education and protocol development, can provide comfort to children in the emergency setting and improve staff and family satisfaction.