bluuebunny/crossref_metadata_2025 huggingface dataset:
Study of vibration welding mechanism
Authors: Kuo C.-W. , Yang S.-M. , Chen J.-H. , Lai G.-H. , Wu W.
Published: July 2008

The study on the vertical and horizontal spot vibration welding of Inconel 690 alloy was carried out to observe the dendrite morphologies and estimate the temperature gradient G and growth rate R under different vibration conditions. The purpose is to further understand the mechanism of microstructure changes under vibration. Based on different temperature distributions along vertical and horizontal directions in the centre of a melting pool, it is found that vertical and horizontal vibrations induce the divergence of the nucleates site and grain growth rate then affect the grain morphologies. Vertical vibration welding creates a coarse dendrite structure with sturdy secondary and tertiary dendrite arms, and the X-ray diffraction (XRD) profile of this structure shows a strong (200) peak. Horizontal vibration welding results in grain refinement and a relatively disordered structure, which is reflected by its low XRD intensity. The study shows that vibration affects the weld structure by improving nucleates and changing growth rate.
Microstructure, hardness and residual stress distribution in maraging steel gas tungsten arc weldments
Authors: Venkata Ramana P. , Madhusudhan Reddy G. , Mohandas T.
Published: July 2008

The distribution of residual stresses due to welding has been studied in maraging steel welds. Gas tungsten arc welding process was used and the effect of filler metal composition on the nature of residual stress distribution has been investigated using X-ray diffraction technique with Cr Kα radiation. Three types of filler materials were used, they include: maraging filler, austenitic stainless steel and medium alloy medium carbon steel filler metal. In the case of maraging steel weld, medium alloy medium carbon filler, the residual stress at the centre of the weld zone was more compressive while, less compressive stresses have been identified in the heat affected zone of the parent metal adjacent to the weld metal. But, in the case of austenitic stainless steel filler the residual stresses at the centre of the weld and heat affected zone were tensile. Post-weld aging treatment reduced the magnitude of stresses. The observed residual stress distribution across the weldments has been correlated with microstructure and hardness distribution across the weld.
Artificial neural network approach for estimating weld bead width and depth of penetration from infrared thermal image of weld pool
Authors: Ghanty P. , Vasudevan M. , Mukherjee D. P. , Pal N. R. , Chandrasekhar N. , Maduraimuthu V. , Bhaduri A. K. , Barat P. , Raj B.
Published: July 2008

In this article an artificial neural network based system to predict weld bead geometry using features derived from the infrared thermal video of a welding process is proposed. The multilayer perceptron and radial basis function networks are used in the prediction model and an online feature selection technique prioritises the features used in the prediction model. The efficacy of the system is demonstrated with a number of welding experiments and using the leave one out cross-validation experiments.
Effect of solidification velocity on weld solidification process of alloy tool steel
Authors: Hashimoto T. , Terasaki H. , Komizo Y.
Published: July 2008

In order to clarify the effect of solidification velocity on the weld solidification process of alloy tool steel during the welding, the information about microstructure evolution was obtained by the concurrent experiments of liquid tin quenching and time resolved X-ray diffraction technique using intense synchrotron radiation. It was found from the experiments that the solidification mode was transferred from an FA to an A mode at the high solidification velocity. The effect of solidification velocity on the phase selection during solidification between the primary δ-ferrite and γ-austenite was theoretically proved by the Kurz, Giovanola and Trivedi (KGT) model. It is thus explained that the solidification cracking susceptibility of the weld metal of alloy tool steel was enhanced due to the δ to γ transition of the primary phase.
Ethnic Marked Names as a Reflection of United States Isolationist Attitudes in Uncle $crooge Comic Books
Authors: Chen Lindsey N.
Published: July 2008

AbstractThis paper examines the ethnic-marked names created by Carl Barks, the writer/artist of one of the most popular Walt Disney comic book series of the 1950s and 1960s. My thesis is that, in the years following World War II, many Americans had isolationist feelings, and one of the reasons for the success of the Uncle $crooge comic books is that they fed into these feelings on almost a subconscious level.
A Slave by Any Other Name: Names and Identity in Toni Morrison's Beloved
Authors: Lyles-Scott Cynthia
Published: July 2008

AbstractNames and naming play an important part in Toni Morrison's Beloved: A Novel, which won the 1987 Pulitzer Prize. The story is set in 1873, a decade after the Civil War, but much of it is told through memories and flashbacks of the time when the main characters, Baby Suggs, Paul D, and Halle, were slaves. Morrison's story demonstrates differences in both intent and result when names were issued by slave owners as opposed to names bestowed by Black people themselves.
Xhosa First Names: A Dual Identity in Harmony or in Conflict?
Authors: Neethling Bertie
Published: July 2008

AbstractXhosa speakers in South Africa often carry a true Xhosa ('ethnic') name as well as an English one. This came about as a result of colonization and the efforts of the missionaries who often bestowed a 'church' or 'school' name upon children. This has become a convention. With the advent of full democracy, one expects that name carriers might develop different perspectives on this convention. It is argued that Xhosa society (and African society broadly speaking) is divided on this issue: although there are indications that the ethnic name is gaining ground over the English one, many name carriers are also quite content with their English names.
Names in Multilingual-Multicultural Malaysia
Authors: Cheng Karen Kow Yip
Published: July 2008

AbstractMalaysia is a multilingual-multicultural country. A study of personal and family names in Malaysia is not only interesting but also profound as this country is composed of three major ethnic groups: Malays, Chinese, and Indians. A name is one of the things that give individuals their own special identity, while also helping others identify the person. The focus of this paper is on ethnicity and names with special reference to Self Identity, Ethnic Identity, and Nation Identity. Factors affecting the above include race, religion, culture, language, dialect, and nationality. Issues that arise from such a study are of great importance not only to the individual but also to the individual as a member of a family and of a particular ethnic group, and at the macro level, as a member of a nation.
How I treat cobalamin (vitamin B12) deficiency
Authors: Carmel Ralph
Published: July 2008

The challenges in medical management of cobalamin deficiency lie in attention to the unique pathophysiology that underlies cobalamin deficiency, more than in the mechanics of therapy. The central physiologic principles are that clinically important deficiency is more likely to occur (and progress) when intrinsic factor–driven absorption fails than when diet is poor and that most causes take years to produce clinically obvious deficiency. Transient defects have little clinical impact. The key management principle is the importance of follow-up, which also requires knowing how the deficiency arose. The virtues of these principles are not always fully appreciated. Recent developments have made diagnosis and management more difficult by diminishing the ability to determine cobalamin absorption status. Clinicians must also grapple with premature medicalization of isolated, mild biochemical changes that added many asymptomatic cases of still undetermined medical relevance to their caseload, often expanded by inflated cobalamin level criteria. The potential for misattribution of cobalamin-unrelated presentations to nongermane cobalamin and metabolite abnormalities has grown. Pathophysiologically based management requires systematic attention to each of its individual components: correctly diagnosing cobalamin deficiency, reversing it, defining its underlying cause, preventing relapse, managing the underlying disorder and its complications, and educating the patient.
Efficient generation of human alloantigen-specific CD4+ regulatory T cells from naive precursors by CD40-activated B cells
Authors: Tu Wenwei , Lau Yu-Lung , Zheng Jian , Liu Yinping , Chan Ping-Lung , Mao Huawei , Dionis Kira , Schneider Pascal , Lewis David B.
Published: July 2008

CD4+CD25+Foxp3+ regulatory T cells (Treg) play an important role in the induction and maintenance of immune tolerance. Although adoptive transfer of bulk populations of Treg can prevent or treat T cell–mediated inflammatory diseases and transplant allograft rejection in animal models, optimal Treg immunotherapy in humans would ideally use antigen-specific rather than polyclonal Treg for greater specificity of regulation and avoidance of general suppression. However, no robust approaches have been reported for the generation of human antigen-specific Treg at a practical scale for clinical use. Here, we report a simple and cost-effective novel method to rapidly induce and expand large numbers of functional human alloantigen-specific Treg from antigenically naive precursors in vitro using allogeneic nontransformed B cells as stimulators. By this approach naive CD4+CD25− T cells could be expanded 8-fold into alloantigen-specific Treg after 3 weeks of culture without any exogenous cytokines. The induced alloantigen-specific Treg were CD45RO+CCR7− memory cells, and had a CD4high, CD25+, Foxp3+, and CD62L (L-selectin)+ phenotype. Although these CD4highCD25+Foxp3+ alloantigen-specific Treg had no cytotoxic capacity, their suppressive function was cell-cell contact dependent and partially relied on cytotoxic T lymphocyte antigen-4 expression. This approach may accelerate the clinical application of Treg-based immunotherapy in transplantation and autoimmune diseases.
Mcl-1 expression has in vitro and in vivo significance in chronic lymphocytic leukemia and is associated with other poor prognostic markers
Authors: Pepper Chris , Lin Thet Thet , Pratt Guy , Hewamana Saman , Brennan Paul , Hiller Louise , Hills Robert , Ward Rachel , Starczynski Jane , Austen Belinda , Hooper Laura , Stankovic Tatjana , Fegan Chris
Published: July 2008

Bcl-2 family proteins play a critical role in the regulation of apoptosis in chronic lymphocytic leukemia (CLL). However, their association with established prognostic markers is unknown. In this study, we analyzed the expression of Bcl-2, Bax, and Mcl-1 in 185 CLL patients and evaluated their relationship with other prognostic markers, in vitro sensitivity to fludarabine, and clinical outcome. Mcl-1 expression was significantly correlated with stage of disease (P < .001), lymphocyte doubling time (P = .01), VH gene mutation status (P < .001), CD38 expression (P < .001), and ZAP-70 expression (P = .003). In addition, Mcl-1 and Mcl-1/Bax ratios showed strong correlations with in vitro resistance to fludarabine (P = .005 and P < .001, respectively). Furthermore, elevated Mcl-1 expression and Mcl-1/Bax ratios were predictive of time to first treatment in the whole cohort (P < .001 and P < .001, respectively) and in stage A patients only (P = .002 and P = .001, respectively). Taken together, our data show that Mcl-1 is a key controller of in vitro drug resistance and is an important regulator of disease progression and outcome in CLL. It therefore represents a promising therapeutic target in this incurable condition. The close correlation between Mcl-1 expression and VH gene mutation status, CD38 expression, and ZAP-70 expression offers a biologic explanation for their association with adverse prognosis.
Timing and deciphering mitochondrial DNA macro-haplogroup R0 variability in Central Europe and Middle East
Authors: Brandstätter Anita , Zimmermann Bettina , Wagner Janine , Göbel Tanja , Röck Alexander W , Salas Antonio , Carracedo Angel , Parson Walther
Published: July 2008

Background

Nearly half of the West Eurasian assemblage of human mitochondrial DNA (mtDNA) is fractioned into numerous sub-lineages of the predominant haplogroup (hg) R0. Several hypotheses have been proposed on the origin and the expansion times of some R0 sub-lineages, which were partially inconsistent with each other. Here we describe the phylogenetic structure and genetic variety of hg R0 in five European populations and one population from the Middle East.

Results

Our analysis of 1,350 mtDNA haplotypes belonging to R0, including entire control region sequences and 45 single nucleotide polymorphisms from the coding region, revealed significant differences in the distribution of different sub-hgs even between geographically closely located regions. Estimates of coalescence times that were derived using diverse algorithmic approaches consistently affirmed that the major expansions of the different R0 hgs occurred in the terminal Pleistocene and early Holocene.

Conclusion

Given an estimated coalescence time of the distinct lineages of 10 – 18 kya, the differences in the distributions could hint to either limited maternal gene flow after the Last Glacial Maximum due to the alpine nature of the regions involved or to a stochastic loss of diversity due to environmental events and/or disease episodes occurred at different times and in distinctive regions. Our comparison of two different ways of obtaining the timing of the most recent common ancestor confirms that the time of a sudden expansion can be adequately recovered from control region data with valid confidence intervals. For reliable estimates, both procedures should be applied in order to cross-check the results for validity and soundness.
Re-annotation of the physical map of Glycine max for polyploid-like regions by BAC end sequence driven whole genome shotgun read assembly
Authors: Saini Navinder , Shultz Jeffry , Lightfoot David A
Published: July 2008

Background

Many of the world's most important food crops have either polyploid genomes or homeologous regions derived from segmental shuffling following polyploid formation. The soybean (Glycine max) genome has been shown to be composed of approximately four thousand short interspersed homeologous regions with 1, 2 or 4 copies per haploid genome by RFLP analysis, microsatellite anchors to BACs and by contigs formed from BAC fingerprints. Despite these similar regions,, the genome has been sequenced by whole genome shotgun sequence (WGS). Here the aim was to use BAC end sequences (BES) derived from three minimum tile paths (MTP) to examine the extent and homogeneity of polyploid-like regions within contigs and the extent of correlation between the polyploid-like regions inferred from fingerprinting and the polyploid-like sequences inferred from WGS matches.

Results

Results show that when sequence divergence was 1–10%, the copy number of homeologous regions could be identified from sequence variation in WGS reads overlapping BES. Homeolog sequence variants (HSVs) were single nucleotide polymorphisms (SNPs; 89%) and single nucleotide indels (SNIs 10%). Larger indels were rare but present (1%). Simulations that had predicted fingerprints of homeologous regions could be separated when divergence exceeded 2% were shown to be false. We show that a 5–10% sequence divergence is necessary to separate homeologs by fingerprinting. BES compared to WGS traces showed polyploid-like regions with less than 1% sequence divergence exist at 2.3% of the locations assayed.

Conclusion

The use of HSVs like SNPs and SNIs to characterize BACs wil improve contig building methods. The implications for bioinformatic and functional annotation of polyploid and paleopolyploid genomes show that a combined approach of BAC fingerprint based physical maps, WGS sequence and HSV-based partitioning of BAC clones from homeologous regions to separate contigs will allow reliable de-convolution and positioning of sequence scaffolds (see BES_scaffolds section of SoyGD). This approach will assist genome annotation for paleopolyploid and true polyploid genomes such as soybean and many important cereal and fruit crops.
Antibody responses to the merozoite surface protein-1 complex in cerebral malaria patients in India
Authors: Lucchi Naomi W , Tongren Jon Eric , Jain Vidhan , Nagpal Avinash C , Kauth Christian W , Woehlbier Ute , Bujard Hermann , Dash Aditya P , Singh Neeru , Stiles Jonathan K , Udhayakumar Venkatachalam
Published: July 2008

Background

Plasmodium falciparuminfection causes cerebral malaria (CM) in a subset of patients with anti-malarial treatment protecting only about 70% to 80% of patients. Why a subset of malaria patients develops CM complications, including neurological sequelae or death, is still not well understood. It is believed that host immune factors may modulate CM outcomes and there is substantial evidence that cellular immune factors, such as cytokines, play an important role in this process. In this study, the potential relationship between the antibody responses to the merozoite surface protein (MSP)-1 complex (which consists of four fragments namely: MSP-183, MSP-130, MSP-138and MSP-142), MSP-636and MSP-722and CM was investigated.

Methods

Peripheral blood antibody responses to recombinant antigens of the two major allelic forms of MSP-1 complex, MSP-636and MSP-722were compared between healthy subjects, mild malaria patients (MM) and CM patients residing in a malaria endemic region of central India. Total IgG and IgG subclass antibody responses were determined using ELISA method.

Results

The prevalence and levels of IgG and its subclasses in the plasma varied for each antigen. In general, the prevalence of total IgG, IgG1 and IgG3 was higher in the MM patients and lower in CM patients compared to healthy controls. Significantly lower levels of total IgG antibodies to the MSP-1f38, IgG1 levels to MSP-1d83, MSP-119and MSP-636and IgG3 levels to MSP-1f42and MSP-722were observed in CM patients as compared to MM patients.

Conclusion

These results suggest that there may be some dysregulation in the generation of antibody responses to some MSP antigens in CM patients and it is worth investigating further whether perturbations of antibody responses in CM patients contribute to pathogenesis.
An in vitro assay of collagen fiber alignment by acupuncture needle rotation
Authors: Julias Margaret , Edgar Lowell T , Buettner Helen M , Shreiber David I
Published: July 2008

Background

During traditional acupuncture therapy, soft tissues attach to and wind around the acupuncture needle. To study this phenomenon in a controlled and quantitative setting, we performed acupuncture needling in vitro.

Methods

Acupuncture was simulated in vitro in three-dimensional, type I collagen gels prepared at 1.5 mg/ml, 2.0 mg/ml, and 2.5 mg/ml collagen, and either crosslinked with formalin or left untreated. Acupuncture needles were inserted into the gels and rotated via a computer-controlled motor at 0.3 rev/sec for up to 10 revolutions while capturing the evolution of birefringence under cross-polarization.

Results

Simulated acupuncture produced circumferential alignment of collagen fibers close to the needle that evolved into radial alignment as the distance from the needle increased, which generally matched observations from published tissue explant studies. All gels failed prior to 10 revolutions, and the location of failure was near the transition between circumferential and radial alignment. Crosslinked collagen failed at a significantly lower number of revolutions than untreated collagen, whereas collagen concentration had no effect on gel failure. The strength of the alignment field increased with increasing collagen concentration and decreased with crosslinking. Separate studies were performed in which the gel thickness and depth of needle insertion were varied. As gel thickness increased, gels failed at fewer needle revolutions. For the same depth of insertion, alignment was greater in thinner gels. Alignment increased as the depth of insertion increased.

Conclusion

These results indicate that the mechanostructural properties of soft connective tissues may affect their response to acupuncture therapy. The in vitro model provides a platform to study mechanotransduction during acupuncture in a highly controlled and quantitative setting.
Estrogen level monitoring in artificial frozen-thawed embryo transfer cycles using step-up regime without pituitary suppression: is it necessary?
Authors: Niu Zhihong , Feng Yun , Sun Yijuan , Zhang Aijun , Zhang Huiqin
Published: July 2008

Background

To discuss the meaning of serum oestradiol monitoring in frozen embryo transfer cycle using hormone replacement without pretreatment with gonadotropin hormone (GnRH) agonist.

Methods

The data from two hundred twelve women undergoing two hundred seventy-four frozen-thawed embryo transfer (FET) cycles was included in this retrospective cohort study. They were detected of serum oestradiol levels and endometrium thicknesses during hormone supplement FET cycles and compared their pregnancy outcomes according to their oestradiol level on progesterone initiation day.

Results

Patients with different levels of serum oestradiol (percentile 0–25th, 25th–75th and 75th–100th) on progesterone initiation day yielded the endometrium thickness of 9.3 ± 0.12, 8.9 ± 0.07 and 9.1 ± 0.11 mm(P > 0.05) and the pregnancy rate of 32.2%, 38.4% and 36.3% (P > 0.05) respectively.

Conclusion

The serum estradiol level did not predict pregnancy success in hormone replacement FET cycles, suggesting that oestradiol monitoring in this method of endometrial preparation is unnecessary.
Tumor slices as a model to evaluate doxorubicin in vitro treatment and expression of trios of genes PRSS11, MTSS1, CLPTM1 and PRSS11, MTSS1, SMYD2 in canine mammary gland cancer
Authors: Sobral Renata A , Honda Suzana T , Katayama Maria Lucia H , Brentani Helena , Brentani M Mitzi , Patrão Diogo FC , Folgueira Maria Aparecida AK
Published: July 2008

Background

In women with breast cancer submitted to neoadjuvant chemotherapy based in doxorubicin, tumor expression of groups of three genes (PRSS11, MTSS1, CLPTM1 and PRSS11, MTSS1, SMYD2) have classified them as responsive or resistant. We have investigated whether expression of these trios of genes could predict mammary carcinoma response in dogs and whether tumor slices, which maintain epithelial-mesenchymal interactions, could be used to evaluate drug response in vitro.

Methods

Tumors from 38 dogs were sliced and cultured with or without doxorubicin 1 μM for 24 h. Tumor cells were counted by two observers to establish a percentage variation in cell number, between slices. Based on these results, a reduction in cell number between treated and control samples ≥ 21.7%, arbitrarily classified samples, as drug responsive. Tumor expression of PRSS11, MTSS1, CLPTM1 and SMYD2, was evaluated by real time PCR. Relative expression results were then transformed to their natural logarithm values, which were spatially disposed according to the expression of trios of genes, comprising PRSS11, MTSS1, CLPTM1 and PRSS11, MTSS1, SMYD2. Fisher linear discrimination test was used to generate a separation plane between responsive and non-responsive tumors.

Results

Culture of tumor slices for 24 h was feasible. Nine samples were considered responsive and 29 non-responsive to doxorubicin, considering the pre-established cut-off value of cell number reduction ≥ 21.7%, between doxorubicin treated and control samples. Relative gene expression was evaluated and tumor samples were then spatially distributed according to the expression of the trios of genes: PRSS11, MTSS1, CLPTM1 and PRSS11, MTSS1, SMYD2. A separation plane was generated. However, no clear separation between responsive and non-responsive samples could be observed.

Conclusion

Three-dimensional distribution of samples according to the expression of the trios of genes PRSS11, MTSS1, CLPTM1 and PRSS11, MTSS1, SMYD2 could not predict doxorubicin in vitro responsiveness. Short term culture of mammary gland cancer slices may be an interesting model to evaluate chemotherapy activity.
Presence and utility of IgA-class antibodies to cyclic citrullinated peptides in early rheumatoid arthritis: the Swedish TIRA project
Authors: Svärd Anna , Kastbom Alf , Reckner-Olsson Åsa , Skogh Thomas
Published: July 2008

Introduction

The present study was carried out to assess whether IgA-class antibodies against cyclic citrullinated peptides (IgA anti-CCP) in recent-onset rheumatoid arthritis add diagnostic and/or prognostic information to IgG anti-CCP analysis.

Methods

Serum samples were obtained from 228 patients with recent-onset (<12 months) rheumatoid arthritis at the time of inclusion in the Swedish TIRA cohort (Swedish Early Intervention in Rheumatoid Arthritis). Sera from 72 of these patients were also available at the 3-year follow-up. Disease activity and functional ability measures (erythrocyte sedimentation rate, serum C-reactive protein, 28-joint count Disease Activity Score, physician's assessment of disease activity, and the Swedish version of the Health Assessment Questionnaire) were registered at inclusion and at regular follow-ups during 3 years. An IgA anti-CCP assay was developed based on the commercially available IgG-specific enzyme immunoassay from EuroDiagnostica (Arnhem, the Netherlands), replacing the detection antibody by an anti-human-IgA antibody. A positive IgA anti-CCP test was defined by the 99th percentile among healthy blood donors.

Results

At baseline, a positive IgA anti-CCP test was observed in 29% of the patient sera, all of which also tested positive for IgG anti-CCP at a higher average level than sera containing IgG anti-CCP alone. The IgA anti-CCP-positive patients had significantly higher disease activity over time compared with the IgA anti-CCP-negative patients. After considering the IgG anti-CCP level, the disease activity also tended to be higher in the IgA anti-CCP-positive cases – although this difference did not reach statistical significance. The proportion of IgA anti-CCP-positive patients was significantly larger among smokers than among nonsmokers.

Conclusion

Anti-CCP antibodies of the IgA class were found in about one-third of patients with recent-onset rheumatoid arthritis, all of whom also had IgG anti-CCP. The occurrence of IgA-class antibodies was associated with smoking, and IgA anti-CCP-positive patients had a more severe disease course over 3 years compared with IgA anti-CCP-negative cases. Although IgA anti-CCP analysis does not seem to offer any diagnostic information in addition to IgG anti-CCP analysis, further efforts are justified to investigate the prognostic implications.
Procalcitonin in liver transplantation: are high levels due to donors or recipients?
Authors: Eyraud Daniel , Ben Ayed Saïd , Tanguy Marie Laure , Vézinet Corinne , Siksik Jean Michel , Bernard Maguy , Fratéa Sylvia , Movschin Marie , Vaillant Jean-Christophe , Coriat Pierre , Hannoun Laurent
Published: July 2008

Introduction

To date, a specific marker to evaluate and predict the clinical course or complication of the liver-transplanted patient is not available in clinical practice. Increased procalcitonin (PCT) levels have been found in infectious inflammation; poor organ perfusion and high PCT levels in the cardiac donor appeared to predict early graft failure. We evaluated PCT as a predictor of early graft dysfunction and postoperative complications.

Methods

PCT serum concentrations were measured in samples collected before organ retrieval from 67 consecutive brain-dead donors and in corresponding recipients from day 0, before liver transplantation, up to day 7 after liver transplantation. The following parameters were recorded in donors: amount of vasopressive drug doses, cardiac arrest history 24 hours before retrieval, number of days in the intensive care unit, age of donor, and infection in donor, and the following parameters were recorded in recipients: cold and warm ischemia time, veno-venous bypass, transfusion amount during orthotopic liver transplantation (OLT), and occurrence of postoperative complication or hepatic dysfunction.

Results

In the donor, the preoperative level of PCT was associated with cardiac arrest and high doses of catecholamines before organ retrieval. In the recipient, elevated PCT levels were observed early after OLT, with a peak at day 1 or 2 after OLT, then a decrease until day 7. A postoperative peak of PCT levels was associated neither with preoperative PCT levels in the donor or the recipients nor with hepatic post-OLT dysfunction or other postoperative complications, but with two donor parameters: infection and cardiac arrest.

Conclusion

PCT level in the donor and early PCT peak in the recipient are not predictive of post-OLT hepatic dysfunction or other complications. Cardiac arrest and infection in the donor, but not PCT level in the donor, are associated with high post-OLT PCT levels in the recipient.
Toward Optimization of Postremission Therapy for Residual Disease–Positive Patients With Acute Myeloid Leukemia
Authors: Maurillo Luca , Buccisano Francesco , Del Principe Maria Ilaria , Del Poeta Giovanni , Spagnoli Alessandra , Panetta Paola , Ammatuna Emanuele , Neri Benedetta , Ottaviani Licia , Sarlo Chiara , Venditti Daniela , Quaresima Micol , Cerretti Raffaella , Rizzo Manuela , de Fabritiis Paolo , Lo Coco Francesco , Arcese William , Amadori Sergio , Venditti Adriano
Published: July 2008

Purpose

Despite the identification of several baseline prognostic indicators, the outcome of patients with acute myeloid leukemia (AML) is generally heterogeneous. The effects of autologous (AuSCT) or allogeneic stem-cell transplantation (SCT) are still under evaluation. Minimal residual disease (MRD) states may be essential for assigning patients to therapy-dependent risk categories.

Patients and Methods

By multiparametric flow cytometry, we assessed the levels of MRD in 142 patients with AML who achieved complete remission after intensive chemotherapy.

Results

A level of 3.5 × 10−4 residual leukemia cells (RLCs) after consolidation therapy was established to identify MRD-negative and MRD-positive cases, with 5-year relapse-free survival (RFS) rates of 60% and 16%, respectively (P < .0001) and overall survival (OS) rates of 62% and 23%, respectively (P = .0001). Of patients (n = 77) who underwent a transplantation procedure (56 AuSCT and 21 SCT procedures); 42 patients (55%) were MRD positive (28 patients who underwent AuSCT and 14 patients who underwent SCT) and 35 patients (45%) were MRD negative (28 patients who underwent AuSCT and seven who underwent SCT). MRD-negative patients had a favorable prognosis, with only eight (22%) of 35 patients experiencing relapse, whereas 29 (69%) of 42 MRD-positive patients experienced relapse (P < .0001). In this high-risk group of 42 patients, we observed that 23 (82%) of 28 of those who underwent AuSCT experienced relapse, whereas six (43%) of 14 who underwent SCT experienced relapse (P = .014). Patients who underwent SCT also had a higher likelihood of RFS (47% v 14%).

Conclusion

A threshold of 3.5 × 10−4 RLCs postconsolidation is critical for predicting disease outcome. MRD-negative patients have a good outcome regardless of the type of transplant they receive. In the MRD-positive group, AuSCT does not improve prognosis and SCT represents the primary option.
Receptor Activity-Modifying Proteins Differentially Modulate the G Protein-Coupling Efficiency of Amylin Receptors
Authors: Morfis Maria , Tilakaratne Nanda , Furness Sebastian G. B. , Christopoulos George , Werry Tim D. , Christopoulos Arthur , Sexton Patrick M.
Published: July 2008

Receptor activity-modifying proteins (RAMPs) 1, 2, and 3 are prototypic G protein-coupled receptor accessory proteins that can alter not only receptor trafficking but also receptor phenotype. Specific RAMP interaction with the calcitonin receptor (CTR) generates novel and distinct receptors for the peptide amylin; however, the role of RAMPs in receptor signaling is not understood. The current study demonstrates that RAMP interaction with the CTRa in COS-7 or HEK-293 cells leads to selective modulation of signaling pathways activated by the receptor complex. There was a 20- to 30-fold induction in amylin potency at CTR/RAMP1 (AMY1) and CTR/RAMP3 (AMY3) receptors, compared with CTR alone, for formation of the second-messenger cAMP that parallels an increase in amylin binding affinity. In contrast, only 2- to 5-fold induction of amylin potency was seen for mobilization of intracellular Ca++ or activation of ERK1/2. In addition, in COS-7 cells, the increase in amylin potency for Ca++ mobilization was 2-fold greater for AMY3 receptors, compared with AMY1 receptors and this paralleled the relative capacity of overexpression of Gαq proteins to augment induction of high affinity 125I-amylin binding. These data demonstrate that RAMP-complexed receptors have a different signaling profile to CTRs expressed in the absence of RAMPs, and this is likely due to direct effects of the RAMP on G protein-coupling efficiency.
Structure Activity Relationships and Differential Interactions and Functional Activity of Various Equine Estrogens Mediated via Estrogen Receptors (ERs) ERα and ERβ
Authors: Bhavnani Bhagu R. , Tam Shui-Pang , Lu XiaoFeng
Published: July 2008

The human estrogen receptors (ERs) α and β interact with 17β-estradiol (17β-E2), estrone, 17α-estradiol, and the ring B unsaturated estrogens, equilin, 17β-dihydroequilin, 17α-dihydroequilin, equilenin, 17β-dihydroequilenin, 17α-dihydroequilenin, Δ8-estrone, and Δ8, 17β-E2 with varying affinities. In comparison to 17β-E2, the relative binding affinities of most ring B unsaturated estrogens were 2- to 8-fold lower for ERα and ERβ, however, some of these unique estrogens had two to four times greater affinity for ERβ than ERα. The transcriptional activity of these estrogens in HepG2 cells transfected with ERα or ERβ, or both, and the secreted-alkaline phosphatase gene showed that all estrogens were functionally active. 17β-E2 induced the activity of secreted-alkaline phosphatase by ERα to a level higher than any other estrogen. Activity of other estrogens was 12–17% that of 17β-E2. In contrast, 17β-E2 stimulated the activity of ERβ to a 5-fold lower level than that with ERα, whereas the activity of other estrogens was 66–290% that of 17β-E2, with equilenin being the most active. The presence of both ER subtypes did not alter the functional activity of 17β-E2, although it further enhanced the activity of 17β-dihydroequilin (200%), 17β-dihydroequilenin (160%), and Δ8, 17β-E2 (130%). Except for 17β-E2, no correlation was observed between the functional activities and their binding affinities for ER. In conclusion, our results show that the effects of ring B unsaturated estrogens are mainly mediated via ERβ and that the presence of both ER subtypes further enhances their activity. It is now possible to develop hormone replacement therapy using selective ring B unsaturated estrogens for target tissues where ERβ is the predominant ER.
ICI 182,780 Penetrates Brain and Hypothalamic Tissue and Has Functional Effects in the Brain after Systemic Dosing
Authors: Alfinito Peter D. , Chen Xiaohong , Atherton James , Cosmi Scott , Deecher Darlene C.
Published: July 2008

Previous reports suggest the antiestrogen ICI 182,780 (ICI) does not cross the blood-brain barrier (BBB). However, this hypothesis has never been directly tested. In the present study, we tested whether ICI crosses the BBB, penetrates into brain and hypothalamic tissues, and affects known neuroendocrine functions in ovariectomized rats. Using HPLC with mass spectrometry, ICI (1.0 mg/kg·d, 3 d) was detected in plasma and brain and hypothalamic tissues for up to 24 h with maximum concentrations of 43.1 ng/ml, and 31.6 and 38.8 ng/g, respectively. To evaluate antiestrogenic effects of ICI in the brain after systemic dosing, we tested its ability to block the effect of 17 α-ethinyl estradiol (EE) (0.3 mg/kg, 8 d) on tail-skin temperature abatement in the morphine-dependent model of hot flush and on body weight change. In the morphine-dependent model, EE abated 64% of the naloxone-induced tail-skin temperature increase. ICI pretreatment (1.0, 3.0 mg/kg·d) dose dependently inhibited this effect. ICI (3.0 mg/kg·d) alone showed estrogenic-like actions, abating 30% the naloxone-induced flush. In body weight studies, EE-treated rats weighed 58.5 g less than vehicle-treated rats after 8 d dosing. This effect was partially blocked by ICI (3.0 mg/kg·d) pretreatment. Similar to EE treatment, rats receiving 1.0 or 3.0 mg/kg·d ICI alone showed little weight gain compared with vehicle-treated controls. Thus, ICI crosses the BBB, penetrates into brain and hypothalamic tissues, and has both antiestrogenic and estrogenic-like actions on neuroendocrine-related functions.
Expression of the Muscle Atrophy Factor Muscle Atrophy F-Box Is Suppressed by Testosterone
Authors: Zhao Weidong , Pan Jiangping , Wang Xiaolei , Wu Yong , Bauman William A. , Cardozo Christopher P.
Published: July 2008

The ubiquitin ligase muscle atrophy F-box (MAFbx; also called atrogin-1) is thought to play important roles in muscle loss. Conversely, testosterone reduces atrophy from glucocorticoids or denervation associated with repression of MAFbx. To characterize mechanisms of such repression, the effects of testosterone on MAFbx expression in C2C12 cells were tested. Testosterone reduced MAFbx mRNA levels as well as expression of a reporter gene under the control of 3.1 kb of the human MAFbx promoter. Repression required the androgen receptor (AR) as well as sequences within the first 208 bases upstream of the first codon of the MAFbx gene. This sequence is downstream of known forkhead transcription factor binding sites and testosterone did not alter Forkhead box O 3A phosphorylation. The AR associated with sequences conferring repression in a manner that was stimulated by testosterone and was independent of DNA binding. In gel shift studies, octamer binding transcription factor (Oct)-1 bound two predicted Oct-1 sites within these sequences. Deletion of Oct-1 sites from reporter genes prevented repression by testosterone. Gene knockdown of Oct-1 blocked repression of MAFbx reporter gene activity by testosterone and binding of AR to sequences conferring repression. In conclusion, testosterone represses MAFbx expression via interactions of the AR with Oct-1 that are associated with sequences within the 5′ untranslated region of the MAFbx promotor located just upstream of the first codon. This action of testosterone may contribute to beneficial actions of testosterone on muscle.
The Orphan Nuclear Receptor NUR77 Regulates Hormone-Induced StAR Transcription in Leydig Cells through Cooperation with Ca2+/Calmodulin-Dependent Protein Kinase I
Authors: Martin Luc J. , Boucher Nicolas , Brousseau Catherine , Tremblay Jacques J.
Published: July 2008

Cholesterol transport in the mitochondrial membrane, an essential step of steroid biosynthesis, is mediated by a protein complex containing the steroidogenic acute regulatory (StAR) protein. The importance of this transporter is underscored by mutations in the human StAR gene that cause lipoid congenital adrenal hyperplasia, male pseudohermaphroditism, and adrenal insufficiency. StAR transcription in steroidogenic cells is hormonally regulated and involves several transcription factors. The nuclear receptor NUR77 is present in steroidogenic cells, and its expression is induced by hormones known to activate StAR expression. We have now established that StAR transcription in cAMP-stimulated Leydig cells requires de novo protein synthesis and involves NUR77. We found that cAMP-induced NUR77 expression precedes that of StAR both at the mRNA and protein levels in Leydig cells. In these cells, small interfering RNA-mediated NUR77 knockdown reduces cAMP-induced StAR expression. Chromatin immunoprecipitation assays revealed a cAMP-dependent increase in NUR77 recruitment to the proximal StAR promoter, whereas transient transfections in MA-10 Leydig cells confirmed that NUR77 can activate the StAR promoter and that this requires an element located at −95 bp. cAMP-induced StAR and NUR77 expression in Leydig cells was found to require a Ca2+/calmodulin-dependent protein kinase (CaMK)-dependent signaling pathway. Consistent with this, we show that within the testis, CaMKI is specifically expressed in Leydig cells. Finally, we report that CaMKI transcriptionally cooperates with NUR77, but not steroidogenic factor 1, to further enhance StAR promoter activity in Leydig cells. All together, our results implicate NUR77 as a mediator of cAMP action on StAR transcription in steroidogenic Leydig cells and identify a role for CaMKI in this process.
Notch signalling is required for both dauer maintenance and recovery inC. elegans
Authors: Ouellet Jimmy , Li Shaolin , Roy Richard
Published: July 2008

The Notch signalling pathway is conserved among higher metazoans and is used repeatedly throughout development to specify distinct cell fates among populations of equipotent cells. Mounting evidence suggests that Notch signalling may also be crucial in neuronal function in postmitotic,differentiated neurons. Here, we demonstrate a novel role for the canonical Notch signalling pathway in postmitotic neurons during a specialised`diapause-like' post-embryonic developmental stage in C. eleganscalled dauer. Our data suggest that cell signalling downstream of the developmental decision to enter dauer leads to the activation of Notch-responding genes in postmitotic neurons. Consistent with this, we demonstrate that glp-1, one of the two C. elegans Notch receptors, and its ligand lag-2 are expressed in neurons during the dauer stage, and both genes are required to maintain this stage in a daf-7/TGFβ dauer constitutive background. Our genetic data also suggest that a second Notch receptor, lin-12, functions upstream of,or in parallel with, insulin-like signalling components in response to replete growth conditions to promote dauer recovery. Based on our findings, cues associated with the onset of dauer ultimately trigger a glp-1-dependent Notch signalling cascade in neurons to maintain this developmental state. Then, as growth conditions improve, activation of the LIN-12 Notch receptor cooperates with the insulin-like signalling pathway to signal recovery from the dauer stage.
ACAULIS5 controlsArabidopsisxylem specification through the prevention of premature cell death
Authors: Muñiz Luis , Minguet Eugenio G. , Singh Sunil Kumar , Pesquet Edouard , Vera-Sirera Francisco , Moreau-Courtois Charleen L. , Carbonell Juan , Blázquez Miguel A. , Tuominen Hannele
Published: July 2008

Cell size and secondary cell wall patterning are crucial for the proper functioning of xylem vessel elements in the vascular tissues of plants. Through detailed anatomical characterization of Arabidopsis thalianahypocotyls, we observed that mutations in the putative spermine biosynthetic gene ACL5 severely affected xylem specification: the xylem vessel elements of the acl5 mutant were small and mainly of the spiral type,and the normally predominant pitted vessels as well as the xylem fibers were completely missing. The cell-specific expression of ACL5 in the early developing vessel elements, as detected by in situ hybridization and reporter gene analyses, suggested that the observed xylem vessel defects were caused directly by the acl5 mutation. Exogenous spermine prolonged xylem element differentiation and stimulated cell expansion and cell wall elaboration in xylogenic cell cultures of Zinnia elegans, suggesting that ACL5 prevents premature death of the developing vessel elements to allow complete expansion and secondary cell wall patterning. This was further supported by our observations that the vessel elements of acl5 seemed to initiate the cell death program too early and that the xylem defects associated with acl5 could be largely phenocopied by induction of premature, diphtheria toxin-mediated cell death in the ACL5-expressing vessel elements. We therefore provide, for the first time, mechanistic evidence for the function of ACL5 in xylem specification through its action on the duration of xylem element differentiation.
Neuregulin-mediated ErbB3 signaling is required for formation of zebrafish dorsal root ganglion neurons
Authors: Honjo Yasuko , Kniss Jonathan , Eisen Judith S.
Published: July 2008

Dorsal root ganglia (DRGs) arise from trunk neural crest cells that emerge from the dorsal neuroepithelium and coalesce into segmental streams that migrate ventrally along the developing somites. Proper formation of DRGs involves not only normal trunk neural crest migration, but also the ability of DRG progenitors to pause at a particular target location where they can receive DRG-promoting signals. In mammalian embryos, a receptor tyrosine kinase proto-oncogene, ErbB3, is required for proper trunk neural crest migration. Here, we show that in zebrafish mutants lacking ErbB3 function,neural crest cells do not pause at the location where DRGs normally form and DRG neurons are not generated. We also show that these mutants lack trunk neural crest-derived sympathetic neurons, but that cranial neural crest-derived enteric neurons appear normal. We isolated three genes encoding neuregulins, ErbB3 ligands, and show that two neuregulins function together in zebrafish trunk neural crest cell migration and in DRG formation. Together,our results suggest that ErbB3 signaling is required for normal migration of trunk, but not cranial, neural crest cells.
Estimating Cycle Time Percentile Curves for Manufacturing Systems via Simulation
Authors: Yang Feng , Ankenman Bruce E. , Nelson Barry L.
Published: July 2008

Cycle time-throughput (CT-TH) percentile curves quantify the relationship between percentiles of cycle time and factory throughput, and they can play an important role in strategic planning for manufacturing systems. In this paper, a highly flexible distribution, the generalized gamma, is used to represent the underlying distribution of cycle time. To obtain CT-TH percentile curves, we use a factory simulation to fit metamodels for the first three CT-TH moment curves throughout the throughput range of interest, determine the parameters of the generalized gamma by matching moments, and obtain any percentile of interest by inverting the distribution. To insure efficiency and control estimation error, simulation experiments are built up sequentially using a multistage procedure. Numerical results are presented to demonstrate the effectiveness of the approach.
Practice Prize Paper—BRAN*EQT: A Multicategory Brand Equity Model and Its Application at Allstate
Authors: Shankar Venkatesh , Azar Pablo , Fuller Matthew
Published: July 2008

We develop a robust model for estimating, tracking, and managing brand equity for multicategory brands based on customer survey and financial measures. This model has two components: (1) offering value (computed from discounted cash flow analysis) and (2) relative brand importance (computed from brand choice models such as multinomial logit, heteroscedastic extreme value, and mixed logit). We apply this model to estimate the brand equity of Allstate—a leading insurance company—and its leading competitor, which compete in multiple categories. The model captures the brand's spillover effects from one category to another. In addition, we identify the dimensions that drive a brand's image, examine the relationships among advertising, brand equity, and shareholder value, and build a decision support simulator for the focal brand. Our model provides reliable estimates of brand equity, and our results show that advertising has a strong long-term positive influence on brand equity, which is significantly positively related to shareholder value. The model, the brand equity estimates, and the decision support simulator are used by key executives across multiple functional areas and have enabled the company to substantially gain by reallocating its advertising resources to improve brand equity and shareholder value, and by offering better guidance to analysts and investors.